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Julia von Blume Receives Innovative Science Accelerator Award

The ISAC award provides seed funding for exceptionally innovative, disruptive (high-risk/high-reward) research relevant to the NIDDK Division of Kidney, Urologic, & Hematologic Diseases that has the potential to lead to groundbreaking or paradigm-shifting results that will change the field. The von Blume lab investigates how neutrophils, frontline defenders against infections, are armed with proteins in distinct granule types. Regulated exocytosis activates them for chemotaxis, phagocytosis, and bacteria eradication. Yet, the molecular mechanisms of granule formation are unclear, limiting treatments for neutropenic disorders. The von Blume lab will investigate molecular mechanisms of neutrophil granule biogenesis that could pave the way for powerful therapeutic strategies. This project will be performed in collaboration with Shangqin Guo’s Yale Stem Cell Center lab.

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Stem cells: past, present, and future

• Wojciech Zakrzewski 1 ,
• Maciej Dobrzyński 2 ,
• Maria Szymonowicz 1 &
• Zbigniew Rybak 1  

Stem Cell Research & Therapy volume  10 , Article number:  68 ( 2019 ) Cite this article

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In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.

Stem cell classification

Stem cells are unspecialized cells of the human body. They are able to differentiate into any cell of an organism and have the ability of self-renewal. Stem cells exist both in embryos and adult cells. There are several steps of specialization. Developmental potency is reduced with each step, which means that a unipotent stem cell is not able to differentiate into as many types of cells as a pluripotent one. This chapter will focus on stem cell classification to make it easier for the reader to comprehend the following chapters.

Totipotent stem cells are able to divide and differentiate into cells of the whole organism. Totipotency has the highest differentiation potential and allows cells to form both embryo and extra-embryonic structures. One example of a totipotent cell is a zygote, which is formed after a sperm fertilizes an egg. These cells can later develop either into any of the three germ layers or form a placenta. After approximately 4 days, the blastocyst’s inner cell mass becomes pluripotent. This structure is the source of pluripotent cells.

Pluripotent stem cells (PSCs) form cells of all germ layers but not extraembryonic structures, such as the placenta. Embryonic stem cells (ESCs) are an example. ESCs are derived from the inner cell mass of preimplantation embryos. Another example is induced pluripotent stem cells (iPSCs) derived from the epiblast layer of implanted embryos. Their pluripotency is a continuum, starting from completely pluripotent cells such as ESCs and iPSCs and ending on representatives with less potency—multi-, oligo- or unipotent cells. One of the methods to assess their activity and spectrum is the teratoma formation assay. iPSCs are artificially generated from somatic cells, and they function similarly to PSCs. Their culturing and utilization are very promising for present and future regenerative medicine.

Multipotent stem cells have a narrower spectrum of differentiation than PSCs, but they can specialize in discrete cells of specific cell lineages. One example is a haematopoietic stem cell, which can develop into several types of blood cells. After differentiation, a haematopoietic stem cell becomes an oligopotent cell. Its differentiation abilities are then restricted to cells of its lineage. However, some multipotent cells are capable of conversion into unrelated cell types, which suggests naming them pluripotent cells.

Oligopotent stem cells can differentiate into several cell types. A myeloid stem cell is an example that can divide into white blood cells but not red blood cells.

Unipotent stem cells are characterized by the narrowest differentiation capabilities and a special property of dividing repeatedly. Their latter feature makes them a promising candidate for therapeutic use in regenerative medicine. These cells are only able to form one cell type, e.g. dermatocytes.

Stem cell biology

A blastocyst is formed after the fusion of sperm and ovum fertilization. Its inner wall is lined with short-lived stem cells, namely, embryonic stem cells. Blastocysts are composed of two distinct cell types: the inner cell mass (ICM), which develops into epiblasts and induces the development of a foetus, and the trophectoderm (TE). Blastocysts are responsible for the regulation of the ICM microenvironment. The TE continues to develop and forms the extraembryonic support structures needed for the successful origin of the embryo, such as the placenta. As the TE begins to form a specialized support structure, the ICM cells remain undifferentiated, fully pluripotent and proliferative [ 1 ]. The pluripotency of stem cells allows them to form any cell of the organism. Human embryonic stem cells (hESCs) are derived from the ICM. During the process of embryogenesis, cells form aggregations called germ layers: endoderm, mesoderm and ectoderm (Fig.  1 ), each eventually giving rise to differentiated cells and tissues of the foetus and, later on, the adult organism [ 2 ]. After hESCs differentiate into one of the germ layers, they become multipotent stem cells, whose potency is limited to only the cells of the germ layer. This process is short in human development. After that, pluripotent stem cells occur all over the organism as undifferentiated cells, and their key abilities are proliferation by the formation of the next generation of stem cells and differentiation into specialized cells under certain physiological conditions.

Oocyte development and formation of stem cells: the blastocoel, which is formed from oocytes, consists of embryonic stem cells that later differentiate into mesodermal, ectodermal, or endodermal cells. Blastocoel develops into the gastrula

Signals that influence the stem cell specialization process can be divided into external, such as physical contact between cells or chemical secretion by surrounding tissue, and internal, which are signals controlled by genes in DNA.

Stem cells also act as internal repair systems of the body. The replenishment and formation of new cells are unlimited as long as an organism is alive. Stem cell activity depends on the organ in which they are in; for example, in bone marrow, their division is constant, although in organs such as the pancreas, division only occurs under special physiological conditions.

Stem cell functional division

Whole-body development.

During division, the presence of different stem cells depends on organism development. Somatic stem cell ESCs can be distinguished. Although the derivation of ESCs without separation from the TE is possible, such a combination has growth limits. Because proliferating actions are limited, co-culture of these is usually avoided.

ESCs are derived from the inner cell mass of the blastocyst, which is a stage of pre-implantation embryo ca. 4 days after fertilization. After that, these cells are placed in a culture dish filled with culture medium. Passage is an inefficient but popular process of sub-culturing cells to other dishes. These cells can be described as pluripotent because they are able to eventually differentiate into every cell type in the organism. Since the beginning of their studies, there have been ethical restrictions connected to the medical use of ESCs in therapies. Most embryonic stem cells are developed from eggs that have been fertilized in an in vitro clinic, not from eggs fertilized in vivo.

Somatic or adult stem cells are undifferentiated and found among differentiated cells in the whole body after development. The function of these cells is to enable the healing, growth, and replacement of cells that are lost each day. These cells have a restricted range of differentiation options. Among many types, there are the following:

Mesenchymal stem cells are present in many tissues. In bone marrow, these cells differentiate mainly into the bone, cartilage, and fat cells. As stem cells, they are an exception because they act pluripotently and can specialize in the cells of any germ layer.

Neural cells give rise to nerve cells and their supporting cells—oligodendrocytes and astrocytes.

Haematopoietic stem cells form all kinds of blood cells: red, white, and platelets.

Skin stem cells form, for example, keratinocytes, which form a protective layer of skin.

The proliferation time of somatic stem cells is longer than that of ESCs. It is possible to reprogram adult stem cells back to their pluripotent state. This can be performed by transferring the adult nucleus into the cytoplasm of an oocyte or by fusion with the pluripotent cell. The same technique was used during cloning of the famous Dolly sheep.

hESCs are involved in whole-body development. They can differentiate into pluripotent, totipotent, multipotent, and unipotent cells (Fig.  2 ) [ 2 ].

Changes in the potency of stem cells in human body development. Potency ranges from pluripotent cells of the blastocyst to unipotent cells of a specific tissue in a human body such as the skin, CNS, or bone marrow. Reversed pluripotency can be achieved by the formation of induced pluripotent stem cells using either octamer-binding transcription factor (Oct4), sex-determining region Y (Sox2), Kruppel-like factor 4 (Klf4), or the Myc gene

Pluripotent cells can be named totipotent if they can additionally form extraembryonic tissues of the embryo. Multipotent cells are restricted in differentiating to each cell type of given tissue. When tissue contains only one lineage of cells, stem cells that form them are called either called oligo- or unipotent.

iPSC quality control and recognition by morphological differences

The comparability of stem cell lines from different individuals is needed for iPSC lines to be used in therapeutics [ 3 ]. Among critical quality procedures, the following can be distinguished:

Short tandem repeat analysis—This is the comparison of specific loci on the DNA of the samples. It is used in measuring an exact number of repeating units. One unit consists of 2 to 13 nucleotides repeating many times on the DNA strand. A polymerase chain reaction is used to check the lengths of short tandem repeats. The genotyping procedure of source tissue, cells, and iPSC seed and master cell banks is recommended.

Identity analysis—The unintentional switching of lines, resulting in other stem cell line contamination, requires rigorous assay for cell line identification.

Residual vector testing—An appearance of reprogramming vectors integrated into the host genome is hazardous, and testing their presence is a mandatory procedure. It is a commonly used procedure for generating high-quality iPSC lines. An acceptable threshold in high-quality research-grade iPSC line collections is ≤ 1 plasmid copies per 100 cells. During the procedure, 2 different regions, common to all plasmids, should be used as specific targets, such as EBNA and CAG sequences [ 3 ]. To accurately represent the test reactions, a standard curve needs to be prepared in a carrier of gDNA from a well-characterized hPSC line. For calculations of plasmid copies per cell, it is crucial to incorporate internal reference gDNA sequences to allow the quantification of, for example, ribonuclease P (RNaseP) or human telomerase reverse transcriptase (hTERT).

Karyotype—A long-term culture of hESCs can accumulate culture-driven mutations [ 4 ]. Because of that, it is crucial to pay additional attention to genomic integrity. Karyotype tests can be performed by resuscitating representative aliquots and culturing them for 48–72 h before harvesting cells for karyotypic analysis. If abnormalities are found within the first 20 karyotypes, the analysis must be repeated on a fresh sample. When this situation is repeated, the line is evaluated as abnormal. Repeated abnormalities must be recorded. Although karyology is a crucial procedure in stem cell quality control, the single nucleotide polymorphism (SNP) array, discussed later, has approximately 50 times higher resolution.

Viral testing—When assessing the quality of stem cells, all tests for harmful human adventitious agents must be performed (e.g. hepatitis C or human immunodeficiency virus). This procedure must be performed in the case of non-xeno-free culture agents.

Bacteriology—Bacterial or fungal sterility tests can be divided into culture- or broth-based tests. All the procedures must be recommended by pharmacopoeia for the jurisdiction in which the work is performed.

Single nucleotide polymorphism arrays—This procedure is a type of DNA microarray that detects population polymorphisms by enabling the detection of subchromosomal changes and the copy-neutral loss of heterozygosity, as well as an indication of cellular transformation. The SNP assay consists of three components. The first is labelling fragmented nucleic acid sequences with fluorescent dyes. The second is an array that contains immobilized allele-specific oligonucleotide (ASO) probes. The last component detects, records, and eventually interprets the signal.

Flow cytometry—This is a technique that utilizes light to count and profile cells in a heterogeneous fluid mixture. It allows researchers to accurately and rapidly collect data from heterogeneous fluid mixtures with live cells. Cells are passed through a narrow channel one by one. During light illumination, sensors detect light emitted or refracted from the cells. The last step is data analysis, compilation and integration into a comprehensive picture of the sample.

Phenotypic pluripotency assays—Recognizing undifferentiated cells is crucial in successful stem cell therapy. Among other characteristics, stem cells appear to have a distinct morphology with a high nucleus to cytoplasm ratio and a prominent nucleolus. Cells appear to be flat with defined borders, in contrast to differentiating colonies, which appear as loosely located cells with rough borders [ 5 ]. It is important that images of ideal and poor quality colonies for each cell line are kept in laboratories, so whenever there is doubt about the quality of culture, it can always be checked according to the representative image. Embryoid body formation or directed differentiation of monolayer cultures to produce cell types representative of all three embryonic germ layers must be performed. It is important to note that colonies cultured under different conditions may have different morphologies [ 6 ].

Histone modification and DNA methylation—Quality control can be achieved by using epigenetic analysis tools such as histone modification or DNA methylation. When stem cells differentiate, the methylation process silences pluripotency genes, which reduces differentiation potential, although other genes may undergo demethylation to become expressed [ 7 ]. It is important to emphasize that stem cell identity, together with its morphological characteristics, is also related to its epigenetic profile [ 8 , 9 ]. According to Brindley [ 10 ], there is a relationship between epigenetic changes, pluripotency, and cell expansion conditions, which emphasizes that unmethylated regions appear to be serum-dependent.

hESC derivation and media

hESCs can be derived using a variety of methods, from classic culturing to laser-assisted methodologies or microsurgery [ 11 ]. hESC differentiation must be specified to avoid teratoma formation (see Fig.  3 ).

Spontaneous differentiation of hESCs causes the formation of a heterogeneous cell population. There is a different result, however, when commitment signals (in forms of soluble factors and culture conditions) are applied and enable the selection of progenitor cells

hESCs spontaneously differentiate into embryonic bodies (EBs) [ 12 ]. EBs can be studied instead of embryos or animals to predict their effects on early human development. There are many different methods for acquiring EBs, such as bioreactor culture [ 13 ], hanging drop culture [ 12 ], or microwell technology [ 14 , 15 ]. These methods allow specific precursors to form in vitro [ 16 ].

The essential part of these culturing procedures is a separation of inner cell mass to culture future hESCs (Fig.  4 ) [ 17 ]. Rosowski et al. [ 18 ] emphasizes that particular attention must be taken in controlling spontaneous differentiation. When the colony reaches the appropriate size, cells must be separated. The occurrence of pluripotent cells lasts for 1–2 days. Because the classical utilization of hESCs caused ethical concerns about gastrulas used during procedures, Chung et al. [ 19 ] found out that it is also possible to obtain hESCs from four cell embryos, leaving a higher probability of embryo survival. Additionally, Zhang et al. [ 20 ] used only in vitro fertilization growth-arrested cells.

Culturing of pluripotent stem cells in vitro. Three days after fertilization, totipotent cells are formed. Blastocysts with ICM are formed on the sixth day after fertilization. Pluripotent stem cells from ICM can then be successfully transmitted on a dish

Cell passaging is used to form smaller clusters of cells on a new culture surface [ 21 ]. There are four important passaging procedures.

Enzymatic dissociation is a cutting action of enzymes on proteins and adhesion domains that bind the colony. It is a gentler method than the manual passage. It is crucial to not leave hESCs alone after passaging. Solitary cells are more sensitive and can easily undergo cell death; collagenase type IV is an example [ 22 , 23 ].

Manual passage , on the other hand, focuses on using cell scratchers. The selection of certain cells is not necessary. This should be done in the early stages of cell line derivation [ 24 ].

Trypsin utilization allows a healthy, automated hESC passage. Good Manufacturing Practice (GMP)-grade recombinant trypsin is widely available in this procedure [ 24 ]. However, there is a risk of decreasing the pluripotency and viability of stem cells [ 25 ]. Trypsin utilization can be halted with an inhibitor of the protein rho-associated protein kinase (ROCK) [ 26 ].

Ethylenediaminetetraacetic acid ( EDTA ) indirectly suppresses cell-to-cell connections by chelating divalent cations. Their suppression promotes cell dissociation [ 27 ].

Stem cells require a mixture of growth factors and nutrients to differentiate and develop. The medium should be changed each day.

Traditional culture methods used for hESCs are mouse embryonic fibroblasts (MEFs) as a feeder layer and bovine serum [ 28 ] as a medium. Martin et al. [ 29 ] demonstrated that hESCs cultured in the presence of animal products express the non-human sialic acid, N -glycolylneuraminic acid (NeuGc). Feeder layers prevent uncontrolled proliferation with factors such as leukaemia inhibitory factor (LIF) [ 30 ].

First feeder layer-free culture can be supplemented with serum replacement, combined with laminin [ 31 ]. This causes stable karyotypes of stem cells and pluripotency lasting for over a year.

Initial culturing media can be serum (e.g. foetal calf serum FCS), artificial replacement such as synthetic serum substitute (SSS), knockout serum replacement (KOSR), or StemPro [ 32 ]. The simplest culture medium contains only eight essential elements: DMEM/F12 medium, selenium, NaHCO 3, l -ascorbic acid, transferrin, insulin, TGFβ1, and FGF2 [ 33 ]. It is not yet fully known whether culture systems developed for hESCs can be allowed without adaptation in iPSC cultures.

Turning point in stem cell therapy

The turning point in stem cell therapy appeared in 2006, when scientists Shinya Yamanaka, together with Kazutoshi Takahashi, discovered that it is possible to reprogram multipotent adult stem cells to the pluripotent state. This process avoided endangering the foetus’ life in the process. Retrovirus-mediated transduction of mouse fibroblasts with four transcription factors (Oct-3/4, Sox2, KLF4, and c-Myc) [ 34 ] that are mainly expressed in embryonic stem cells could induce the fibroblasts to become pluripotent (Fig.  5 ) [ 35 ]. This new form of stem cells was named iPSCs. One year later, the experiment also succeeded with human cells [ 36 ]. After this success, the method opened a new field in stem cell research with a generation of iPSC lines that can be customized and biocompatible with the patient. Recently, studies have focused on reducing carcinogenesis and improving the conduction system.

Retroviral-mediated transduction induces pluripotency in isolated patient somatic cells. Target cells lose their role as somatic cells and, once again, become pluripotent and can differentiate into any cell type of human body

The turning point was influenced by former discoveries that happened in 1962 and 1987.

The former discovery was about scientist John Gurdon successfully cloning frogs by transferring a nucleus from a frog’s somatic cells into an oocyte. This caused a complete reversion of somatic cell development [ 37 ]. The results of his experiment became an immense discovery since it was previously believed that cell differentiation is a one-way street only, but his experiment suggested the opposite and demonstrated that it is even possible for a somatic cell to again acquire pluripotency [ 38 ].

The latter was a discovery made by Davis R.L. that focused on fibroblast DNA subtraction. Three genes were found that originally appeared in myoblasts. The enforced expression of only one of the genes, named myogenic differentiation 1 (Myod1), caused the conversion of fibroblasts into myoblasts, showing that reprogramming cells is possible, and it can even be used to transform cells from one lineage to another [ 39 ].

Although pluripotency can occur naturally only in embryonic stem cells, it is possible to induce terminally differentiated cells to become pluripotent again. The process of direct reprogramming converts differentiated somatic cells into iPSC lines that can form all cell types of an organism. Reprogramming focuses on the expression of oncogenes such as Myc and Klf4 (Kruppel-like factor 4). This process is enhanced by a downregulation of genes promoting genome stability, such as p53. Additionally, cell reprogramming involves histone alteration. All these processes can cause potential mutagenic risk and later lead to an increased number of mutations. Quinlan et al. [ 40 ] checked fully pluripotent mouse iPSCs using whole genome DNA sequencing and structural variation (SV) detection algorithms. Based on those studies, it was confirmed that although there were single mutations in the non-genetic region, there were non-retrotransposon insertions. This led to the conclusion that current reprogramming methods can produce fully pluripotent iPSCs without severe genomic alterations.

During the course of development from pluripotent hESCs to differentiated somatic cells, crucial changes appear in the epigenetic structure of these cells. There is a restriction or permission of the transcription of genes relevant to each cell type. When somatic cells are being reprogrammed using transcription factors, all the epigenetic architecture has to be reconditioned to achieve iPSCs with pluripotency [ 41 ]. However, cells of each tissue undergo specific somatic genomic methylation. This influences transcription, which can further cause alterations in induced pluripotency [ 42 ].

Source of iPSCs

Because pluripotent cells can propagate indefinitely and differentiate into any kind of cell, they can be an unlimited source, either for replacing lost or diseased tissues. iPSCs bypass the need for embryos in stem cell therapy. Because they are made from the patient’s own cells, they are autologous and no longer generate any risk of immune rejection.

At first, fibroblasts were used as a source of iPSCs. Because a biopsy was needed to achieve these types of cells, the technique underwent further research. Researchers investigated whether more accessible cells could be used in the method. Further, other cells were used in the process: peripheral blood cells, keratinocytes, and renal epithelial cells found in urine. An alternative strategy to stem cell transplantation can be stimulating a patient’s endogenous stem cells to divide or differentiate, occurring naturally when skin wounds are healing. In 2008, pancreatic exocrine cells were shown to be reprogrammed to functional, insulin-producing beta cells [ 43 ].

The best stem cell source appears to be the fibroblasts, which is more tempting in the case of logistics since its stimulation can be fast and better controlled [ 44 ].

• Teratoma formation assay

The self-renewal and differentiation capabilities of iPSCs have gained significant interest and attention in regenerative medicine sciences. To study their abilities, a quality-control assay is needed, of which one of the most important is the teratoma formation assay. Teratomas are benign tumours. Teratomas are capable of rapid growth in vivo and are characteristic because of their ability to develop into tissues of all three germ layers simultaneously. Because of the high pluripotency of teratomas, this formation assay is considered an assessment of iPSC’s abilities [ 45 ].

Teratoma formation rate, for instance, was observed to be elevated in human iPSCs compared to that in hESCs [ 46 ]. This difference may be connected to different differentiation methods and cell origins. Most commonly, the teratoma assay involves an injection of examined iPSCs subcutaneously or under the testis or kidney capsule in mice, which are immune-deficient [ 47 ]. After injection, an immature but recognizable tissue can be observed, such as the kidney tubules, bone, cartilage, or neuroepithelium [ 30 ]. The injection site may have an impact on the efficiency of teratoma formation [ 48 ].

There are three groups of markers used in this assay to differentiate the cells of germ layers. For endodermal tissue, there is insulin/C-peptide and alpha-1 antitrypsin [ 49 ]. For the mesoderm, derivatives can be used, e.g. cartilage matrix protein for the bone and alcian blue for the cartilage. As ectodermal markers, class III B botulin or keratin can be used for keratinocytes.

Teratoma formation assays are considered the gold standard for demonstrating the pluripotency of human iPSCs, demonstrating their possibilities under physiological conditions. Due to their actual tissue formation, they could be used for the characterization of many cell lineages [ 50 ].

Directed differentiation

To be useful in therapy, stem cells must be converted into desired cell types as necessary or else the whole regenerative medicine process will be pointless. Differentiation of ESCs is crucial because undifferentiated ESCs can cause teratoma formation in vivo. Understanding and using signalling pathways for differentiation is an important method in successful regenerative medicine. In directed differentiation, it is likely to mimic signals that are received by cells when they undergo successive stages of development [ 51 ]. The extracellular microenvironment plays a significant role in controlling cell behaviour. By manipulating the culture conditions, it is possible to restrict specific differentiation pathways and generate cultures that are enriched in certain precursors in vitro. However, achieving a similar effect in vivo is challenging. It is crucial to develop culture conditions that will allow the promotion of homogenous and enhanced differentiation of ESCs into functional and desired tissues.

Regarding the self-renewal of embryonic stem cells, Hwang et al. [ 52 ] noted that the ideal culture method for hESC-based cell and tissue therapy would be a defined culture free of either the feeder layer or animal components. This is because cell and tissue therapy requires the maintenance of large quantities of undifferentiated hESCs, which does not make feeder cells suitable for such tasks.

Most directed differentiation protocols are formed to mimic the development of an inner cell mass during gastrulation. During this process, pluripotent stem cells differentiate into ectodermal, mesodermal, or endodermal progenitors. Mall molecules or growth factors induce the conversion of stem cells into appropriate progenitor cells, which will later give rise to the desired cell type. There is a variety of signal intensities and molecular families that may affect the establishment of germ layers in vivo, such as fibroblast growth factors (FGFs) [ 53 ]; the Wnt family [ 54 ] or superfamily of transforming growth factors—β(TGFβ); and bone morphogenic proteins (BMP) [ 55 ]. Each candidate factor must be tested on various concentrations and additionally applied to various durations because the precise concentrations and times during which developing cells in embryos are influenced during differentiation are unknown. For instance, molecular antagonists of endogenous BMP and Wnt signalling can be used for ESC formation of ectoderm [ 56 ]. However, transient Wnt and lower concentrations of the TGFβ family trigger mesodermal differentiation [ 57 ]. Regarding endoderm formation, a higher activin A concentration may be required [ 58 , 59 ].

There are numerous protocols about the methods of forming progenitors of cells of each of germ layers, such as cardiomyocytes [ 60 ], hepatocytes [ 61 ], renal cells [ 62 ], lung cells [ 63 , 64 ], motor neurons [ 65 ], intestinal cells [ 66 ], or chondrocytes [ 67 ].

Directed differentiation of either iPSCs or ESCs into, e.g. hepatocytes, could influence and develop the study of the molecular mechanisms in human liver development. In addition, it could also provide the possibility to form exogenous hepatocytes for drug toxicity testing [ 68 ].

Levels of concentration and duration of action with a specific signalling molecule can cause a variety of factors. Unfortunately, for now, a high cost of recombinant factors is likely to limit their use on a larger scale in medicine. The more promising technique focuses on the use of small molecules. These can be used for either activating or deactivating specific signalling pathways. They enhance reprogramming efficiency by creating cells that are compatible with the desired type of tissue. It is a cheaper and non-immunogenic method.

One of the successful examples of small-molecule cell therapies is antagonists and agonists of the Hedgehog pathway. They show to be very useful in motor neuron regeneration [ 69 ]. Endogenous small molecules with their function in embryonic development can also be used in in vitro methods to induce the differentiation of cells; for example, retinoic acid, which is responsible for patterning the nervous system in vivo [ 70 ], surprisingly induced retinal cell formation when the laboratory procedure involved hESCs [ 71 ].

The efficacy of differentiation factors depends on functional maturity, efficiency, and, finally, introducing produced cells to their in vivo equivalent. Topography, shear stress, and substrate rigidity are factors influencing the phenotype of future cells [ 72 ].

The control of biophysical and biochemical signals, the biophysical environment, and a proper guide of hESC differentiation are important factors in appropriately cultured stem cells.

Stem cell utilization and their manufacturing standards and culture systems

The European Medicines Agency and the Food and Drug Administration have set Good Manufacturing Practice (GMP) guidelines for safe and appropriate stem cell transplantation. In the past, protocols used for stem cell transplantation required animal-derived products [ 73 ].

The risk of introducing animal antigens or pathogens caused a restriction in their use. Due to such limitations, the technique required an obvious update [ 74 ]. Now, it is essential to use xeno-free equivalents when establishing cell lines that are derived from fresh embryos and cultured from human feeder cell lines [ 75 ]. In this method, it is crucial to replace any non-human materials with xeno-free equivalents [ 76 ].

NutriStem with LN-511, TeSR2 with human recombinant laminin (LN-511), and RegES with human foreskin fibroblasts (HFFs) are commonly used xeno-free culture systems [ 33 ]. There are many organizations and international initiatives, such as the National Stem Cell Bank, that provide stem cell lines for treatment or medical research [ 77 ].

Stem cell use in medicine

Stem cells have great potential to become one of the most important aspects of medicine. In addition to the fact that they play a large role in developing restorative medicine, their study reveals much information about the complex events that happen during human development.

The difference between a stem cell and a differentiated cell is reflected in the cells’ DNA. In the former cell, DNA is arranged loosely with working genes. When signals enter the cell and the differentiation process begins, genes that are no longer needed are shut down, but genes required for the specialized function will remain active. This process can be reversed, and it is known that such pluripotency can be achieved by interaction in gene sequences. Takahashi and Yamanaka [ 78 ] and Loh et al. [ 79 ] discovered that octamer-binding transcription factor 3 and 4 (Oct3/4), sex determining region Y (SRY)-box 2 and Nanog genes function as core transcription factors in maintaining pluripotency. Among them, Oct3/4 and Sox2 are essential for the generation of iPSCs.

Many serious medical conditions, such as birth defects or cancer, are caused by improper differentiation or cell division. Currently, several stem cell therapies are possible, among which are treatments for spinal cord injury, heart failure [ 80 ], retinal and macular degeneration [ 81 ], tendon ruptures, and diabetes type 1 [ 82 ]. Stem cell research can further help in better understanding stem cell physiology. This may result in finding new ways of treating currently incurable diseases.

Haematopoietic stem cell transplantation

Haematopoietic stem cells are important because they are by far the most thoroughly characterized tissue-specific stem cell; after all, they have been experimentally studied for more than 50 years. These stem cells appear to provide an accurate paradigm model system to study tissue-specific stem cells, and they have potential in regenerative medicine.

Multipotent haematopoietic stem cell (HSC) transplantation is currently the most popular stem cell therapy. Target cells are usually derived from the bone marrow, peripheral blood, or umbilical cord blood [ 83 ]. The procedure can be autologous (when the patient’s own cells are used), allogenic (when the stem cell comes from a donor), or syngeneic (from an identical twin). HSCs are responsible for the generation of all functional haematopoietic lineages in blood, including erythrocytes, leukocytes, and platelets. HSC transplantation solves problems that are caused by inappropriate functioning of the haematopoietic system, which includes diseases such as leukaemia and anaemia. However, when conventional sources of HSC are taken into consideration, there are some important limitations. First, there is a limited number of transplantable cells, and an efficient way of gathering them has not yet been found. There is also a problem with finding a fitting antigen-matched donor for transplantation, and viral contamination or any immunoreactions also cause a reduction in efficiency in conventional HSC transplantations. Haematopoietic transplantation should be reserved for patients with life-threatening diseases because it has a multifactorial character and can be a dangerous procedure. iPSC use is crucial in this procedure. The use of a patient’s own unspecialized somatic cells as stem cells provides the greatest immunological compatibility and significantly increases the success of the procedure.

Stem cells as a target for pharmacological testing

Stem cells can be used in new drug tests. Each experiment on living tissue can be performed safely on specific differentiated cells from pluripotent cells. If any undesirable effect appears, drug formulas can be changed until they reach a sufficient level of effectiveness. The drug can enter the pharmacological market without harming any live testers. However, to test the drugs properly, the conditions must be equal when comparing the effects of two drugs. To achieve this goal, researchers need to gain full control of the differentiation process to generate pure populations of differentiated cells.

Stem cells as an alternative for arthroplasty

One of the biggest fears of professional sportsmen is getting an injury, which most often signifies the end of their professional career. This applies especially to tendon injuries, which, due to current treatment options focusing either on conservative or surgical treatment, often do not provide acceptable outcomes. Problems with the tendons start with their regeneration capabilities. Instead of functionally regenerating after an injury, tendons merely heal by forming scar tissues that lack the functionality of healthy tissues. Factors that may cause this failed healing response include hypervascularization, deposition of calcific materials, pain, or swelling [ 84 ].

Additionally, in addition to problems with tendons, there is a high probability of acquiring a pathological condition of joints called osteoarthritis (OA) [ 85 ]. OA is common due to the avascular nature of articular cartilage and its low regenerative capabilities [ 86 ]. Although arthroplasty is currently a common procedure in treating OA, it is not ideal for younger patients because they can outlive the implant and will require several surgical procedures in the future. These are situations where stem cell therapy can help by stopping the onset of OA [ 87 ]. However, these procedures are not well developed, and the long-term maintenance of hyaline cartilage requires further research.

Osteonecrosis of the femoral hip (ONFH) is a refractory disease associated with the collapse of the femoral head and risk of hip arthroplasty in younger populations [ 88 ]. Although total hip arthroplasty (THA) is clinically successful, it is not ideal for young patients, mostly due to the limited lifetime of the prosthesis. An increasing number of clinical studies have evaluated the therapeutic effect of stem cells on ONFH. Most of the authors demonstrated positive outcomes, with reduced pain, improved function, or avoidance of THA [ 89 , 90 , 91 ].

Rejuvenation by cell programming

Ageing is a reversible epigenetic process. The first cell rejuvenation study was published in 2011 [ 92 ]. Cells from aged individuals have different transcriptional signatures, high levels of oxidative stress, dysfunctional mitochondria, and shorter telomeres than in young cells [ 93 ]. There is a hypothesis that when human or mouse adult somatic cells are reprogrammed to iPSCs, their epigenetic age is virtually reset to zero [ 94 ]. This was based on an epigenetic model, which explains that at the time of fertilization, all marks of parenteral ageing are erased from the zygote’s genome and its ageing clock is reset to zero [ 95 ].

In their study, Ocampo et al. [ 96 ] used Oct4, Sox2, Klf4, and C-myc genes (OSKM genes) and affected pancreas and skeletal muscle cells, which have poor regenerative capacity. Their procedure revealed that these genes can also be used for effective regenerative treatment [ 97 ]. The main challenge of their method was the need to employ an approach that does not use transgenic animals and does not require an indefinitely long application. The first clinical approach would be preventive, focused on stopping or slowing the ageing rate. Later, progressive rejuvenation of old individuals can be attempted. In the future, this method may raise some ethical issues, such as overpopulation, leading to lower availability of food and energy.

For now, it is important to learn how to implement cell reprogramming technology in non-transgenic elder animals and humans to erase marks of ageing without removing the epigenetic marks of cell identity.

Cell-based therapies

Stem cells can be induced to become a specific cell type that is required to repair damaged or destroyed tissues (Fig.  6 ). Currently, when the need for transplantable tissues and organs outweighs the possible supply, stem cells appear to be a perfect solution for the problem. The most common conditions that benefit from such therapy are macular degenerations [ 98 ], strokes [ 99 ], osteoarthritis [ 89 , 90 ], neurodegenerative diseases, and diabetes [ 100 ]. Due to this technique, it can become possible to generate healthy heart muscle cells and later transplant them to patients with heart disease.

Stem cell experiments on animals. These experiments are one of the many procedures that proved stem cells to be a crucial factor in future regenerative medicine

In the case of type 1 diabetes, insulin-producing cells in the pancreas are destroyed due to an autoimmunological reaction. As an alternative to transplantation therapy, it can be possible to induce stem cells to differentiate into insulin-producing cells [ 101 ].

Stem cells and tissue banks

iPS cells with their theoretically unlimited propagation and differentiation abilities are attractive for the present and future sciences. They can be stored in a tissue bank to be an essential source of human tissue used for medical examination. The problem with conventional differentiated tissue cells held in the laboratory is that their propagation features diminish after time. This does not occur in iPSCs.

The umbilical cord is known to be rich in mesenchymal stem cells. Due to its cryopreservation immediately after birth, its stem cells can be successfully stored and used in therapies to prevent the future life-threatening diseases of a given patient.

Stem cells of human exfoliated deciduous teeth (SHED) found in exfoliated deciduous teeth has the ability to develop into more types of body tissues than other stem cells [ 102 ] (Table  1 ). Techniques of their collection, isolation, and storage are simple and non-invasive. Among the advantages of banking, SHED cells are:

Guaranteed donor-match autologous transplant that causes no immune reaction and rejection of cells [ 103 ]

Simple and painless for both child and parent

Less than one third of the cost of cord blood storage

Not subject to the same ethical concerns as embryonic stem cells [ 104 ]

In contrast to cord blood stem cells, SHED cells are able to regenerate into solid tissues such as connective, neural, dental, or bone tissue [ 105 , 106 ]

SHED can be useful for close relatives of the donor

Fertility diseases

In 2011, two researchers, Katsuhiko Hayashi et al. [ 107 ], showed in an experiment on mice that it is possible to form sperm from iPSCs. They succeeded in delivering healthy and fertile pups in infertile mice. The experiment was also successful for female mice, where iPSCs formed fully functional eggs .

Young adults at risk of losing their spermatogonial stem cells (SSC), mostly cancer patients, are the main target group that can benefit from testicular tissue cryopreservation and autotransplantation. Effective freezing methods for adult and pre-pubertal testicular tissue are available [ 108 ].

Qiuwan et al. [ 109 ] provided important evidence that human amniotic epithelial cell (hAEC) transplantation could effectively improve ovarian function by inhibiting cell apoptosis and reducing inflammation in injured ovarian tissue of mice, and it could be a promising strategy for the management of premature ovarian failure or insufficiency in female cancer survivors.

For now, reaching successful infertility treatments in humans appears to be only a matter of time, but there are several challenges to overcome. First, the process needs to have high efficiency; second, the chances of forming tumours instead of eggs or sperm must be maximally reduced. The last barrier is how to mature human sperm and eggs in the lab without transplanting them to in vivo conditions, which could cause either a tumour risk or an invasive procedure.

Therapy for incurable neurodegenerative diseases

Thanks to stem cell therapy, it is possible not only to delay the progression of incurable neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease (AD), and Huntington disease, but also, most importantly, to remove the source of the problem. In neuroscience, the discovery of neural stem cells (NSCs) has nullified the previous idea that adult CNS were not capable of neurogenesis [ 110 , 111 ]. Neural stem cells are capable of improving cognitive function in preclinical rodent models of AD [ 112 , 113 , 114 ]. Awe et al. [ 115 ] clinically derived relevant human iPSCs from skin punch biopsies to develop a neural stem cell-based approach for treating AD. Neuronal degeneration in Parkinson’s disease (PD) is focal, and dopaminergic neurons can be efficiently generated from hESCs. PD is an ideal disease for iPSC-based cell therapy [ 116 ]. However, this therapy is still in an experimental phase ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539501 /). Brain tissue from aborted foetuses was used on patients with Parkinson’s disease [ 117 ]. Although the results were not uniform, they showed that therapies with pure stem cells are an important and achievable therapy.

Stem cell use in dentistry

Teeth represent a very challenging material for regenerative medicine. They are difficult to recreate because of their function in aspects such as articulation, mastication, or aesthetics due to their complicated structure. Currently, there is a chance for stem cells to become more widely used than synthetic materials. Teeth have a large advantage of being the most natural and non-invasive source of stem cells.

For now, without the use of stem cells, the most common periodontological treatments are either growth factors, grafts, or surgery. For example, there are stem cells in periodontal ligament [ 118 , 119 ], which are capable of differentiating into osteoblasts or cementoblasts, and their functions were also assessed in neural cells [ 120 ]. Tissue engineering is a successful method for treating periodontal diseases. Stem cells of the root apical areas are able to recreate periodontal ligament. One of the possible methods of tissue engineering in periodontology is gene therapy performed using adenoviruses-containing growth factors [ 121 ].

As a result of animal studies, dentin regeneration is an effective process that results in the formation of dentin bridges [ 122 ].

Enamel is more difficult to regenerate than dentin. After the differentiation of ameloblastoma cells into the enamel, the former is destroyed, and reparation is impossible. Medical studies have succeeded in differentiating bone marrow stem cells into ameloblastoma [ 123 ].

Healthy dental tissue has a high amount of regular stem cells, although this number is reduced when tissue is either traumatized or inflamed [ 124 ]. There are several dental stem cell groups that can be isolated (Fig.  7 ).

Localization of stem cells in dental tissues. Dental pulp stem cells (DPSCs) and human deciduous teeth stem cells (SHED) are located in the dental pulp. Periodontal ligaments stem cells are located in the periodontal ligament. Apical papilla consists of stem cells from the apical papilla (SCAP)

Dental pulp stem cell (DPSC)

These were the first dental stem cells isolated from the human dental pulp, which were [ 125 ] located inside dental pulp (Table  2 ). They have osteogenic and chondrogenic potential. Mesenchymal stem cells (MSCs) of the dental pulp, when isolated, appear highly clonogenic; they can be isolated from adult tissue (e.g. bone marrow, adipose tissue) and foetal (e.g. umbilical cord) [ 126 ] tissue, and they are able to differentiate densely [ 127 ]. MSCs differentiate into odontoblast-like cells and osteoblasts to form dentin and bone. Their best source locations are the third molars [ 125 ]. DPSCs are the most useful dental source of tissue engineering due to their easy surgical accessibility, cryopreservation possibility, increased production of dentin tissues compared to non-dental stem cells, and their anti-inflammatory abilities. These cells have the potential to be a source for maxillofacial and orthopaedic reconstructions or reconstructions even beyond the oral cavity. DPSCs are able to generate all structures of the developed tooth [ 128 ]. In particular, beneficial results in the use of DPSCs may be achieved when combined with other new therapies, such as periodontal tissue photobiomodulation (laser stimulation), which is an efficient technique in the stimulation of proliferation and differentiation into distinct cell types [ 129 ]. DPSCs can be induced to form neural cells to help treat neurological deficits.

Stem cells of human exfoliated deciduous teeth (SHED) have a faster rate of proliferation than DPSCs and differentiate into an even greater number of cells, e.g. other mesenchymal and non-mesenchymal stem cell derivatives, such as neural cells [ 130 ]. These cells possess one major disadvantage: they form a non-complete dentin/pulp-like complex in vivo. SHED do not undergo the same ethical concerns as embryonic stem cells. Both DPSCs and SHED are able to form bone-like tissues in vivo [ 131 ] and can be used for periodontal, dentin, or pulp regeneration. DPSCs and SHED can be used in treating, for example, neural deficits [ 132 ]. DPSCs alone were tested and successfully applied for alveolar bone and mandible reconstruction [ 133 ].

Periodontal ligament stem cells (PDLSCs)

These cells are used in periodontal ligament or cementum tissue regeneration. They can differentiate into mesenchymal cell lineages to produce collagen-forming cells, adipocytes, cementum tissue, Sharpey’s fibres, and osteoblast-like cells in vitro. PDLSCs exist both on the root and alveolar bone surfaces; however, on the latter, these cells have better differentiation abilities than on the former [ 134 ]. PDLSCs have become the first treatment for periodontal regeneration therapy because of their safety and efficiency [ 135 , 136 ].

Stem cells from apical papilla (SCAP)

These cells are mesenchymal structures located within immature roots. They are isolated from human immature permanent apical papilla. SCAP are the source of odontoblasts and cause apexogenesis. These stem cells can be induced in vitro to form odontoblast-like cells, neuron-like cells, or adipocytes. SCAP have a higher capacity of proliferation than DPSCs, which makes them a better choice for tissue regeneration [ 137 , 138 ].

Dental follicle stem cells (DFCs)

These cells are loose connective tissues surrounding the developing tooth germ. DFCs contain cells that can differentiate into cementoblasts, osteoblasts, and periodontal ligament cells [ 139 , 140 ]. Additionally, these cells proliferate after even more than 30 passages [ 141 ]. DFCs are most commonly extracted from the sac of a third molar. When DFCs are combined with a treated dentin matrix, they can form a root-like tissue with a pulp-dentin complex and eventually form tooth roots [ 141 ]. When DFC sheets are induced by Hertwig’s epithelial root sheath cells, they can produce periodontal tissue; thus, DFCs represent a very promising material for tooth regeneration [ 142 ].

Pulp regeneration in endodontics

Dental pulp stem cells can differentiate into odontoblasts. There are few methods that enable the regeneration of the pulp.

The first is an ex vivo method. Proper stem cells are grown on a scaffold before they are implanted into the root channel [ 143 ].

The second is an in vivo method. This method focuses on injecting stem cells into disinfected root channels after the opening of the in vivo apex. Additionally, the use of a scaffold is necessary to prevent the movement of cells towards other tissues. For now, only pulp-like structures have been created successfully.

Methods of placing stem cells into the root channel constitute are either soft scaffolding [ 144 ] or the application of stem cells in apexogenesis or apexification. Immature teeth are the best source [ 145 ]. Nerve and blood vessel network regeneration are extremely vital to keep pulp tissue healthy.

The potential of dental stem cells is mainly regarding the regeneration of damaged dentin and pulp or the repair of any perforations; in the future, it appears to be even possible to generate the whole tooth. Such an immense success would lead to the gradual replacement of implant treatments. Mandibulary and maxillary defects can be one of the most complicated dental problems for stem cells to address.

Acquiring non-dental tissue cells by dental stem cell differentiation

In 2013, it was reported that it is possible to grow teeth from stem cells obtained extra-orally, e.g. from urine [ 146 ]. Pluripotent stem cells derived from human urine were induced and generated tooth-like structures. The physical properties of the structures were similar to natural ones except for hardness [ 127 ]. Nonetheless, it appears to be a very promising technique because it is non-invasive and relatively low-cost, and somatic cells can be used instead of embryonic cells. More importantly, stem cells derived from urine did not form any tumours, and the use of autologous cells reduces the chances of rejection [ 147 ].

Use of graphene in stem cell therapy

Over recent years, graphene and its derivatives have been increasingly used as scaffold materials to mediate stem cell growth and differentiation [ 148 ]. Both graphene and graphene oxide (GO) represent high in-plane stiffness [ 149 ]. Because graphene has carbon and aromatic network, it works either covalently or non-covalently with biomolecules; in addition to its superior mechanical properties, graphene offers versatile chemistry. Graphene exhibits biocompatibility with cells and their proper adhesion. It also tested positively for enhancing the proliferation or differentiation of stem cells [ 148 ]. After positive experiments, graphene revealed great potential as a scaffold and guide for specific lineages of stem cell differentiation [ 150 ]. Graphene has been successfully used in the transplantation of hMSCs and their guided differentiation to specific cells. The acceleration skills of graphene differentiation and division were also investigated. It was discovered that graphene can serve as a platform with increased adhesion for both growth factors and differentiation chemicals. It was also discovered that π-π binding was responsible for increased adhesion and played a crucial role in inducing hMSC differentiation [ 150 ].

Therapeutic potential of extracellular vesicle-based therapies

Extracellular vesicles (EVs) can be released by virtually every cell of an organism, including stem cells [ 151 ], and are involved in intercellular communication through the delivery of their mRNAs, lipids, and proteins. As Oh et al. [ 152 ] prove, stem cells, together with their paracrine factors—exosomes—can become potential therapeutics in the treatment of, e.g. skin ageing. Exosomes are small membrane vesicles secreted by most cells (30–120 nm in diameter) [ 153 ]. When endosomes fuse with the plasma membrane, they become exosomes that have messenger RNAs (mRNAs) and microRNAs (miRNAs), some classes of non-coding RNAs (IncRNAs) and several proteins that originate from the host cell [ 154 ]. IncRNAs can bind to specific loci and create epigenetic regulators, which leads to the formation of epigenetic modifications in recipient cells. Because of this feature, exosomes are believed to be implicated in cell-to-cell communication and the progression of diseases such as cancer [ 155 ]. Recently, many studies have also shown the therapeutic use of exosomes derived from stem cells, e.g. skin damage and renal or lung injuries [ 156 ].

In skin ageing, the most important factor is exposure to UV light, called “photoageing” [ 157 ], which causes extrinsic skin damage, characterized by dryness, roughness, irregular pigmentation, lesions, and skin cancers. In intrinsic skin ageing, on the other hand, the loss of elasticity is a characteristic feature. The skin dermis consists of fibroblasts, which are responsible for the synthesis of crucial skin elements, such as procollagen or elastic fibres. These elements form either basic framework extracellular matrix constituents of the skin dermis or play a major role in tissue elasticity. Fibroblast efficiency and abundance decrease with ageing [ 158 ]. Stem cells can promote the proliferation of dermal fibroblasts by secreting cytokines such as platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), and basic fibroblast growth factor. Huh et al. [ 159 ] mentioned that a medium of human amniotic fluid-derived stem cells (hAFSC) positively affected skin regeneration after longwave UV-induced (UVA, 315–400 nm) photoageing by increasing the proliferation and migration of dermal fibroblasts. It was discovered that, in addition to the induction of fibroblast physiology, hAFSC transplantation also improved diseases in cases of renal pathology, various cancers, or stroke [ 160 , 161 ].

Oh [ 162 ] also presented another option for the treatment of skin wounds, either caused by physical damage or due to diabetic ulcers. Induced pluripotent stem cell-conditioned medium (iPSC-CM) without any animal-derived components induced dermal fibroblast proliferation and migration.

Natural cutaneous wound healing is divided into three steps: haemostasis/inflammation, proliferation, and remodelling. During the crucial step of proliferation, fibroblasts migrate and increase in number, indicating that it is a critical step in skin repair, and factors such as iPSC-CM that impact it can improve the whole cutaneous wound healing process. Paracrine actions performed by iPSCs are also important for this therapeutic effect [ 163 ]. These actions result in the secretion of cytokines such as TGF-β, interleukin (IL)-6, IL-8, monocyte chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and basic fibroblast growth factor (bFGF). Bae et al. [ 164 ] mentioned that TGF-β induced the migration of keratinocytes. It was also demonstrated that iPSC factors can enhance skin wound healing in vivo and in vitro when Zhou et al. [ 165 ] enhanced wound healing, even after carbon dioxide laser resurfacing in an in vivo study.

Peng et al. [ 166 ] investigated the effects of EVs derived from hESCs on in vitro cultured retinal glial, progenitor Müller cells, which are known to differentiate into retinal neurons. EVs appear heterogeneous in size and can be internalized by cultured Müller cells, and their proteins are involved in the induction and maintenance of stem cell pluripotency. These stem cell-derived vesicles were responsible for the neuronal trans-differentiation of cultured Müller cells exposed to them. However, the research article points out that the procedure was accomplished only on in vitro acquired retina.

Challenges concerning stem cell therapy

Although stem cells appear to be an ideal solution for medicine, there are still many obstacles that need to be overcome in the future. One of the first problems is ethical concern.

The most common pluripotent stem cells are ESCs. Therapies concerning their use at the beginning were, and still are, the source of ethical conflicts. The reason behind it started when, in 1998, scientists discovered the possibility of removing ESCs from human embryos. Stem cell therapy appeared to be very effective in treating many, even previously incurable, diseases. The problem was that when scientists isolated ESCs in the lab, the embryo, which had potential for becoming a human, was destroyed (Fig.  8 ). Because of this, scientists, seeing a large potential in this treatment method, focused their efforts on making it possible to isolate stem cells without endangering their source—the embryo.

Use of inner cell mass pluripotent stem cells and their stimulation to differentiate into desired cell types

For now, while hESCs still remain an ethically debatable source of cells, they are potentially powerful tools to be used for therapeutic applications of tissue regeneration. Because of the complexity of stem cell control systems, there is still much to be learned through observations in vitro. For stem cells to become a popular and widely accessible procedure, tumour risk must be assessed. The second problem is to achieve successful immunological tolerance between stem cells and the patient’s body. For now, one of the best ideas is to use the patient’s own cells and devolve them into their pluripotent stage of development.

New cells need to have the ability to fully replace lost or malfunctioning natural cells. Additionally, there is a concern about the possibility of obtaining stem cells without the risk of morbidity or pain for either the patient or the donor. Uncontrolled proliferation and differentiation of cells after implementation must also be assessed before its use in a wide variety of regenerative procedures on living patients [ 167 ].

One of the arguments that limit the use of iPSCs is their infamous role in tumourigenicity. There is a risk that the expression of oncogenes may increase when cells are being reprogrammed. In 2008, a technique was discovered that allowed scientists to remove oncogenes after a cell achieved pluripotency, although it is not efficient yet and takes a longer amount of time. The process of reprogramming may be enhanced by deletion of the tumour suppressor gene p53, but this gene also acts as a key regulator of cancer, which makes it impossible to remove in order to avoid more mutations in the reprogrammed cell. The low efficiency of the process is another problem, which is progressively becoming reduced with each year. At first, the rate of somatic cell reprogramming in Yamanaka’s study was up to 0.1%. The use of transcription factors creates a risk of genomic insertion and further mutation of the target cell genome. For now, the only ethically acceptable operation is an injection of hESCs into mouse embryos in the case of pluripotency evaluation [ 168 ].

Stem cell obstacles in the future

Pioneering scientific and medical advances always have to be carefully policed in order to make sure they are both ethical and safe. Because stem cell therapy already has a large impact on many aspects of life, it should not be treated differently.

Currently, there are several challenges concerning stem cells. First, the most important one is about fully understanding the mechanism by which stem cells function first in animal models. This step cannot be avoided. For the widespread, global acceptance of the procedure, fear of the unknown is the greatest challenge to overcome.

The efficiency of stem cell-directed differentiation must be improved to make stem cells more reliable and trustworthy for a regular patient. The scale of the procedure is another challenge. Future stem cell therapies may be a significant obstacle. Transplanting new, fully functional organs made by stem cell therapy would require the creation of millions of working and biologically accurate cooperating cells. Bringing such complicated procedures into general, widespread regenerative medicine will require interdisciplinary and international collaboration.

The identification and proper isolation of stem cells from a patient’s tissues is another challenge. Immunological rejection is a major barrier to successful stem cell transplantation. With certain types of stem cells and procedures, the immune system may recognize transplanted cells as foreign bodies, triggering an immune reaction resulting in transplant or cell rejection.

One of the ideas that can make stem cells a “failsafe” is about implementing a self-destruct option if they become dangerous. Further development and versatility of stem cells may cause reduction of treatment costs for people suffering from currently incurable diseases. When facing certain organ failure, instead of undergoing extraordinarily expensive drug treatment, the patient would be able to utilize stem cell therapy. The effect of a successful operation would be immediate, and the patient would avoid chronic pharmacological treatment and its inevitable side effects.

Although these challenges facing stem cell science can be overwhelming, the field is making great advances each day. Stem cell therapy is already available for treating several diseases and conditions. Their impact on future medicine appears to be significant.

After several decades of experiments, stem cell therapy is becoming a magnificent game changer for medicine. With each experiment, the capabilities of stem cells are growing, although there are still many obstacles to overcome. Regardless, the influence of stem cells in regenerative medicine and transplantology is immense. Currently, untreatable neurodegenerative diseases have the possibility of becoming treatable with stem cell therapy. Induced pluripotency enables the use of a patient’s own cells. Tissue banks are becoming increasingly popular, as they gather cells that are the source of regenerative medicine in a struggle against present and future diseases. With stem cell therapy and all its regenerative benefits, we are better able to prolong human life than at any time in history.

Abbreviations

Basic fibroblast growth factor

Bone morphogenic proteins

Dental follicle stem cells

Dental pulp stem cells

Embryonic bodies

Embryonic stem cells

Fibroblast growth factors

Good Manufacturing Practice

Graphene oxide

Human amniotic fluid-derived stem cells

Human embryonic stem cells

Human foreskin fibroblasts

Inner cell mass

Non-coding RNA

Induced pluripotent stem cells

In vitro fertilization

Knockout serum replacement

Leukaemia inhibitory factor

Monocyte chemotactic protein-1

Fibroblasts

Messenger RNA

Mesenchymal stem cells of dental pulp

Myogenic differentiation

Osteoarthritis

Octamer-binding transcription factor 3 and 4

Platelet-derived growth factor

Platelet-derived growth factor-AA

Periodontal ligament stem cells

Rho-associated protein kinase

Stem cells from apical papilla

Stem cells of human exfoliated deciduous teeth

Synthetic Serum Substitute

Trophectoderm

Vascular endothelial growth factor

Transforming growth factors

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Wojciech Zakrzewski, Maria Szymonowicz & Zbigniew Rybak

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Zakrzewski, W., Dobrzyński, M., Szymonowicz, M. et al. Stem cells: past, present, and future. Stem Cell Res Ther 10 , 68 (2019). https://doi.org/10.1186/s13287-019-1165-5

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Research performed at IRR aims to develop new treatments for major diseases. Students on the programme will choose their research projects from a pool of projects proposed by group leaders at IRR. Projects will span the breadth of research areas at IRR and range from fundamental science to clinical and industrial translation projects. It is envisaged that some of the PhD projects will arise from rotation projects undertaken by the students in their first year.

At IRR's Centre for Regenerative Medicine (CRM),  research is focused on understanding disease and the damage they do to the body, and on developing treatments to repair this damage.

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Group leaders at IRR work across stem cell biology, regenerative medicine, reprogramming, inflammation and tissue repair topics. They study multiple diseases, including cancer, heart disease, liver failure, diabetes, and degenerative diseases such as multiple sclerosis and Parkinson's disease.

Research projects undertaken by postgraduate students at IRR in recent years include:

Stem cell and developmental biology

• Investigating the effect of liver stem cell derived signals on neutrophils during liver regeneration
• Micropatterns for modelling trunk development initiation in hESC colonies
• Comparison of human oligodendrocytes derived from ES cells and in human adult brain
• Reinnervation of healing skin wounds: the interaction between nerves and cutaneous stem cells
• Lineage decisions of embryonic stem cells: exploring the links between morphogenesis and differentiation
• Emergence of haematopoietic stem cells in the human embryo: gene expression analysis

The role of the planar cell polarity protein Vangl2 in haematopoietic stem cell emergence

• Generation of fluorescent reporter hESC line for analysis of human haematopoietic stem cell development
• Dissecting the role of Sox2 in pluripotency
• Understanding movements, growth and lineages in a new model of early human spinal development

Inferring the role of human fetal liver stromal niche in the support of human fetal hematopoiesis by cell-to-cell signalling networks analysis on single-cell transcriptomics

Tracking cell cycle during haematopietic progenitor development

Bone marrow osteogenic mesenchymal stem cell potential and prostate cancer metastasis

Role of embryonic macrophages in the haematopoietic stem cell regenerative niche

Tissue homeostasis, remodelling and repair

• Dissecting how T-regulatory cells maintain liver tissue stem cell fate
• The role of direct cell-cell contacts in cancer initiation and early progression
• Creating new tools to monitor and manipulate cell interactions
• Dissecting macrophage subpopulations in tissue regeneration and repair using fluorescence microscopy
• Role of senescent cells in loss of function of the irradiation-injured salivary gland
• Synthetic biology tools for interrogating cell-cell interactions
• Elucidating the mechanisms underpinning vascular regeneration in the zebrafish heart
• Defining the role of the neutrophil in paracetamol-induced liver injury and regeneration
• Exploration of inflammatory cell function during tumour initiation and tail fin regeneration in zebrafish larvae
• The role of white matter damage and endothelial dysfunction in cerebral small vessel disease
• Targeting ageing in the skin through the primary cilia
• Identification of cellular mechanisms that protect the heart against pathological fibrosis and death post-injury
• Cellular sensing and responses in the ageing niche

Understanding how airway macrophages orchestrate tissue repair in the lung through an EGR2-dependent programme

Investigating whether pericyte contraction is controlled by the sympathetic nervous system in the hematopoietic niche.

Molecular mechanisms of ageing in skin: where does senescence start?

Identification of small molecule cocktails that promote human hepatic progenitor cell differentiation

Modelling non-alcoholic fatty liver disease (NAFLD) using human chemically reprogrammed liver progenitors

• Optimising differentiation condition of chemically reprogrammed liver progenitors (CLiPs)
• Defining lineage plasticity of bile duct cells using transcriptomics and epigenomics
• Reprogramming roadblocks during iPSC generation
• Role of paracrine senescence in the differentiation of hepatic progenitor cells into functional hepatocytes
• Reprogramming of leukaemia-associated macrophages: A new approach to fight MLL-AF9 infant leukaemia

Identification and assessment of new candidate genes involved in liver progenitor cell differentiation

• Single-cell RNA Seq analysis of human chemically induced liver progenitor (HCLiP)-derived spheroids
• Reprogramming adult human hepatocytes into progenitors with unlimited proliferation and efficient differentiation capacities
• Role of intestinal macrophage subsets in health, inflammation and repair
• The influence of resident cell senescence on macrophage phenotype
• Determining changes in immune cell populations and extracellular matrix composition contributing to the pathology of radiation-induced hypothyroidism
• Using computational modelling to predict metabolic nodes that dictate neutrophil function in the tissues
• Cellular sensing and regulation via the Hippo pathway
• Computational modelling of immune cell interactions in nerve regeneration
• Understanding resident macrophage autonomy during inflammation
• The role of macrophage phagocytosis in spinal cord regeneration
• Regulation of macrophage polarisation by healthy and fibrotic extracellular matrix in skin

Prototyping and Immune cell recognition using AI

Investigating how T regulatory cells affect bile duct regeneration during liver injury

Clinical manufacture of cells for treatment of diabetic ulcers

Optimising transfection efficiency in primary macrophages for cell therapy

• Protein expression by scar-forming cells in biliary fibrosis
• Investigating the role of oligodendrocyte ‘states’ to improve remyelination in MS
• Macrophages derived in vitro from human pluripotent stem cells: a tool to manipulate macrophage phenotype and function and a potential source of cells for therapy
• Driving human Kupffer cell differentiation using stem cell-derived liver tissue niches
• Deciphering the interplay between macrophages and senescent cells in injury and regeneration following radiotherapy
• Establishing a platform to investigate hepatic immune responses using human chemically reprogrammed liver progenitors (hCLiPS)

Investigate the role of human pericytes in age-related macular degeneration in vitro.

The role of mitochondria in gut epithelial regeneration in Crohn's and Ulcerative Colitis using a human intestinal organoid culture system

Investigating novel technologies to optimise and improve the clinical islet isolation process

Identification of synthetic super-enhances for neuronal gene therapy

Optimization of induced pluripotent stem cell (iPSC) pro-survival compounds for development of iPSC derived cell therapies

Education During Coronavirus

A Smithsonian magazine special report

Science | June 15, 2020

Seventy-Five Scientific Research Projects You Can Contribute to Online

From astrophysicists to entomologists, many researchers need the help of citizen scientists to sift through immense data collections

Rachael Lallensack

Former Assistant Editor, Science and Innovation

If you find yourself tired of streaming services, reading the news or video-chatting with friends, maybe you should consider becoming a citizen scientist. Though it’s true that many field research projects are paused , hundreds of scientists need your help sifting through wildlife camera footage and images of galaxies far, far away, or reading through diaries and field notes from the past.

Plenty of these tools are free and easy enough for children to use. You can look around for projects yourself on Smithsonian Institution’s citizen science volunteer page , National Geographic ’s list of projects and CitizenScience.gov ’s catalog of options. Zooniverse is a platform for online-exclusive projects , and Scistarter allows you to restrict your search with parameters, including projects you can do “on a walk,” “at night” or “on a lunch break.”

To save you some time, Smithsonian magazine has compiled a collection of dozens of projects you can take part in from home.

American Wildlife

If being home has given you more time to look at wildlife in your own backyard, whether you live in the city or the country, consider expanding your view, by helping scientists identify creatures photographed by camera traps. Improved battery life, motion sensors, high-resolution and small lenses have made camera traps indispensable tools for conservation.These cameras capture thousands of images that provide researchers with more data about ecosystems than ever before.

Smithsonian Conservation Biology Institute’s eMammal platform , for example, asks users to identify animals for conservation projects around the country. Currently, eMammal is being used by the Woodland Park Zoo ’s Seattle Urban Carnivore Project, which studies how coyotes, foxes, raccoons, bobcats and other animals coexist with people, and the Washington Wolverine Project, an effort to monitor wolverines in the face of climate change. Identify urban wildlife for the Chicago Wildlife Watch , or contribute to wilderness projects documenting North American biodiversity with The Wilds' Wildlife Watch in Ohio , Cedar Creek: Eyes on the Wild in Minnesota , Michigan ZoomIN , Western Montana Wildlife and Snapshot Wisconsin .

"Spend your time at home virtually exploring the Minnesota backwoods,” writes the lead researcher of the Cedar Creek: Eyes on the Wild project. “Help us understand deer dynamics, possum populations, bear behavior, and keep your eyes peeled for elusive wolves!"

If being cooped up at home has you daydreaming about traveling, Snapshot Safari has six active animal identification projects. Try eyeing lions, leopards, cheetahs, wild dogs, elephants, giraffes, baobab trees and over 400 bird species from camera trap photos taken in South African nature reserves, including De Hoop Nature Reserve and Madikwe Game Reserve .

With South Sudan DiversityCam , researchers are using camera traps to study biodiversity in the dense tropical forests of southwestern South Sudan. Part of the Serenegeti Lion Project, Snapshot Serengeti needs the help of citizen scientists to classify millions of camera trap images of species traveling with the wildebeest migration.

Classify all kinds of monkeys with Chimp&See . Count, identify and track giraffes in northern Kenya . Watering holes host all kinds of wildlife, but that makes the locales hotspots for parasite transmission; Parasite Safari needs volunteers to help figure out which animals come in contact with each other and during what time of year.

Mount Taranaki in New Zealand is a volcanic peak rich in native vegetation, but native wildlife, like the North Island brown kiwi, whio/blue duck and seabirds, are now rare—driven out by introduced predators like wild goats, weasels, stoats, possums and rats. Estimate predator species compared to native wildlife with Taranaki Mounga by spotting species on camera trap images.

The Zoological Society of London’s (ZSL) Instant Wild app has a dozen projects showcasing live images and videos of wildlife around the world. Look for bears, wolves and lynx in Croatia ; wildcats in Costa Rica’s Osa Peninsula ; otters in Hampshire, England ; and both black and white rhinos in the Lewa-Borana landscape in Kenya.

Under the Sea

Researchers use a variety of technologies to learn about marine life and inform conservation efforts. Take, for example, Beluga Bits , a research project focused on determining the sex, age and pod size of beluga whales visiting the Churchill River in northern Manitoba, Canada. With a bit of training, volunteers can learn how to differentiate between a calf, a subadult (grey) or an adult (white)—and even identify individuals using scars or unique pigmentation—in underwater videos and images. Beluga Bits uses a “ beluga boat ,” which travels around the Churchill River estuary with a camera underneath it, to capture the footage and collect GPS data about the whales’ locations.

Many of these online projects are visual, but Manatee Chat needs citizen scientists who can train their ear to decipher manatee vocalizations. Researchers are hoping to learn what calls the marine mammals make and when—with enough practice you might even be able to recognize the distinct calls of individual animals.

Several groups are using drone footage to monitor seal populations. Seals spend most of their time in the water, but come ashore to breed. One group, Seal Watch , is analyzing time-lapse photography and drone images of seals in the British territory of South Georgia in the South Atlantic. A team in Antarctica captured images of Weddell seals every ten minutes while the seals were on land in spring to have their pups. The Weddell Seal Count project aims to find out what threats—like fishing and climate change—the seals face by monitoring changes in their population size. Likewise, the Año Nuevo Island - Animal Count asks volunteers to count elephant seals, sea lions, cormorants and more species on a remote research island off the coast of California.

With Floating Forests , you’ll sift through 40 years of satellite images of the ocean surface identifying kelp forests, which are foundational for marine ecosystems, providing shelter for shrimp, fish and sea urchins. A project based in southwest England, Seagrass Explorer , is investigating the decline of seagrass beds. Researchers are using baited cameras to spot commercial fish in these habitats as well as looking out for algae to study the health of these threatened ecosystems. Search for large sponges, starfish and cold-water corals on the deep seafloor in Sweden’s first marine park with the Koster seafloor observatory project.

The Smithsonian Environmental Research Center needs your help spotting invasive species with Invader ID . Train your eye to spot groups of organisms, known as fouling communities, that live under docks and ship hulls, in an effort to clean up marine ecosystems.

If art history is more your speed, two Dutch art museums need volunteers to start “ fishing in the past ” by analyzing a collection of paintings dating from 1500 to 1700. Each painting features at least one fish, and an interdisciplinary research team of biologists and art historians wants you to identify the species of fish to make a clearer picture of the “role of ichthyology in the past.”

Interesting Insects

Notes from Nature is a digitization effort to make the vast resources in museums’ archives of plants and insects more accessible. Similarly, page through the University of California Berkeley’s butterfly collection on CalBug to help researchers classify these beautiful critters. The University of Michigan Museum of Zoology has already digitized about 300,000 records, but their collection exceeds 4 million bugs. You can hop in now and transcribe their grasshopper archives from the last century . Parasitic arthropods, like mosquitos and ticks, are known disease vectors; to better locate these critters, the Terrestrial Parasite Tracker project is working with 22 collections and institutions to digitize over 1.2 million specimens—and they’re 95 percent done . If you can tolerate mosquito buzzing for a prolonged period of time, the HumBug project needs volunteers to train its algorithm and develop real-time mosquito detection using acoustic monitoring devices. It’s for the greater good!

For the Birders

Birdwatching is one of the most common forms of citizen science . Seeing birds in the wilderness is certainly awe-inspiring, but you can birdwatch from your backyard or while walking down the sidewalk in big cities, too. With Cornell University’s eBird app , you can contribute to bird science at any time, anywhere. (Just be sure to remain a safe distance from wildlife—and other humans, while we social distance ). If you have safe access to outdoor space—a backyard, perhaps—Cornell also has a NestWatch program for people to report observations of bird nests. Smithsonian’s Migratory Bird Center has a similar Neighborhood Nest Watch program as well.

Birdwatching is easy enough to do from any window, if you’re sheltering at home, but in case you lack a clear view, consider these online-only projects. Nest Quest currently has a robin database that needs volunteer transcribers to digitize their nest record cards.

You can also pitch in on a variety of efforts to categorize wildlife camera images of burrowing owls , pelicans , penguins (new data coming soon!), and sea birds . Watch nest cam footage of the northern bald ibis or greylag geese on NestCams to help researchers learn about breeding behavior.

Or record the coloration of gorgeous feathers across bird species for researchers at London’s Natural History Museum with Project Plumage .

Pretty Plants

If you’re out on a walk wondering what kind of plants are around you, consider downloading Leafsnap , an electronic field guide app developed by Columbia University, the University of Maryland and the Smithsonian Institution. The app has several functions. First, it can be used to identify plants with its visual recognition software. Secondly, scientists can learn about the “ the ebb and flow of flora ” from geotagged images taken by app users.

What is older than the dinosaurs, survived three mass extinctions and still has a living relative today? Ginko trees! Researchers at Smithsonian’s National Museum of Natural History are studying ginko trees and fossils to understand millions of years of plant evolution and climate change with the Fossil Atmospheres project . Using Zooniverse, volunteers will be trained to identify and count stomata, which are holes on a leaf’s surface where carbon dioxide passes through. By counting these holes, or quantifying the stomatal index, scientists can learn how the plants adapted to changing levels of carbon dioxide. These results will inform a field experiment conducted on living trees in which a scientist is adjusting the level of carbon dioxide for different groups.

Help digitize and categorize millions of botanical specimens from natural history museums, research institutions and herbaria across the country with the Notes from Nature Project . Did you know North America is home to a variety of beautiful orchid species? Lend botanists a handby typing handwritten labels on pressed specimens or recording their geographic and historic origins for the New York Botanical Garden’s archives. Likewise, the Southeastern U.S. Biodiversity project needs assistance labeling pressed poppies, sedums, valerians, violets and more. Groups in California , Arkansas , Florida , Texas and Oklahoma all invite citizen scientists to partake in similar tasks.

Historic Women in Astronomy

Become a transcriber for Project PHaEDRA and help researchers at the Harvard-Smithsonian Center for Astrophysics preserve the work of Harvard’s women “computers” who revolutionized astronomy in the 20th century. These women contributed more than 130 years of work documenting the night sky, cataloging stars, interpreting stellar spectra, counting galaxies, and measuring distances in space, according to the project description .

More than 2,500 notebooks need transcription on Project PhaEDRA - Star Notes . You could start with Annie Jump Cannon , for example. In 1901, Cannon designed a stellar classification system that astronomers still use today. Cecilia Payne discovered that stars are made primarily of hydrogen and helium and can be categorized by temperature. Two notebooks from Henrietta Swan Leavitt are currently in need of transcription. Leavitt, who was deaf, discovered the link between period and luminosity in Cepheid variables, or pulsating stars, which “led directly to the discovery that the Universe is expanding,” according to her bio on Star Notes .

Volunteers are also needed to transcribe some of these women computers’ notebooks that contain references to photographic glass plates . These plates were used to study space from the 1880s to the 1990s. For example, in 1890, Williamina Flemming discovered the Horsehead Nebula on one of these plates . With Star Notes, you can help bridge the gap between “modern scientific literature and 100 years of astronomical observations,” according to the project description . Star Notes also features the work of Cannon, Leavitt and Dorrit Hoffleit , who authored the fifth edition of the Bright Star Catalog, which features 9,110 of the brightest stars in the sky.

Microscopic Musings

Electron microscopes have super-high resolution and magnification powers—and now, many can process images automatically, allowing teams to collect an immense amount of data. Francis Crick Institute’s Etch A Cell - Powerhouse Hunt project trains volunteers to spot and trace each cell’s mitochondria, a process called manual segmentation. Manual segmentation is a major bottleneck to completing biological research because using computer systems to complete the work is still fraught with errors and, without enough volunteers, doing this work takes a really long time.

For the Monkey Health Explorer project, researchers studying the social behavior of rhesus monkeys on the tiny island Cayo Santiago off the southeastern coast of Puerto Rico need volunteers to analyze the monkeys’ blood samples. Doing so will help the team understand which monkeys are sick and which are healthy, and how the animals’ health influences behavioral changes.

Using the Zooniverse’s app on a phone or tablet, you can become a “ Science Scribbler ” and assist researchers studying how Huntington disease may change a cell’s organelles. The team at the United Kingdom's national synchrotron , which is essentially a giant microscope that harnesses the power of electrons, has taken highly detailed X-ray images of the cells of Huntington’s patients and needs help identifying organelles, in an effort to see how the disease changes their structure.

Oxford University’s Comprehensive Resistance Prediction for Tuberculosis: an International Consortium—or CRyPTIC Project , for short, is seeking the aid of citizen scientists to study over 20,000 TB infection samples from around the world. CRyPTIC’s citizen science platform is called Bash the Bug . On the platform, volunteers will be trained to evaluate the effectiveness of antibiotics on a given sample. Each evaluation will be checked by a scientist for accuracy and then used to train a computer program, which may one day make this process much faster and less labor intensive.

Out of This World

If you’re interested in contributing to astronomy research from the comfort and safety of your sidewalk or backyard, check out Globe at Night . The project monitors light pollution by asking users to try spotting constellations in the night sky at designated times of the year . (For example, Northern Hemisphere dwellers should look for the Bootes and Hercules constellations from June 13 through June 22 and record the visibility in Globe at Night’s app or desktop report page .)

For the amateur astrophysicists out there, the opportunities to contribute to science are vast. NASA's Wide-field Infrared Survey Explorer (WISE) mission is asking for volunteers to search for new objects at the edges of our solar system with the Backyard Worlds: Planet 9 project .

Galaxy Zoo on Zooniverse and its mobile app has operated online citizen science projects for the past decade. According to the project description, there are roughly one hundred billion galaxies in the observable universe. Surprisingly, identifying different types of galaxies by their shape is rather easy. “If you're quick, you may even be the first person to see the galaxies you're asked to classify,” the team writes.

With Radio Galaxy Zoo: LOFAR , volunteers can help identify supermassive blackholes and star-forming galaxies. Galaxy Zoo: Clump Scout asks users to look for young, “clumpy” looking galaxies, which help astronomers understand galaxy evolution.

If current events on Earth have you looking to Mars, perhaps you’d be interested in checking out Planet Four and Planet Four: Terrains —both of which task users with searching and categorizing landscape formations on Mars’ southern hemisphere. You’ll scroll through images of the Martian surface looking for terrain types informally called “spiders,” “baby spiders,” “channel networks” and “swiss cheese.”

Gravitational waves are telltale ripples in spacetime, but they are notoriously difficult to measure. With Gravity Spy , citizen scientists sift through data from Laser Interferometer Gravitational­-Wave Observatory, or LIGO , detectors. When lasers beamed down 2.5-mile-long “arms” at these facilities in Livingston, Louisiana and Hanford, Washington are interrupted, a gravitational wave is detected. But the detectors are sensitive to “glitches” that, in models, look similar to the astrophysical signals scientists are looking for. Gravity Spy teaches citizen scientists how to identify fakes so researchers can get a better view of the real deal. This work will, in turn, train computer algorithms to do the same.

Similarly, the project Supernova Hunters needs volunteers to clear out the “bogus detections of supernovae,” allowing researchers to track the progression of actual supernovae. In Hubble Space Telescope images, you can search for asteroid tails with Hubble Asteroid Hunter . And with Planet Hunters TESS , which teaches users to identify planetary formations, you just “might be the first person to discover a planet around a nearby star in the Milky Way,” according to the project description.

Help astronomers refine prediction models for solar storms, which kick up dust that impacts spacecraft orbiting the sun, with Solar Stormwatch II. Thanks to the first iteration of the project, astronomers were able to publish seven papers with their findings.

With Mapping Historic Skies , identify constellations on gorgeous celestial maps of the sky covering a span of 600 years from the Adler Planetarium collection in Chicago. Similarly, help fill in the gaps of historic astronomy with Astronomy Rewind , a project that aims to “make a holistic map of images of the sky.”

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Rachael Lallensack | READ MORE

Rachael Lallensack is the former assistant web editor for science and innovation at Smithsonian .

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Five Stem Cell Projects Funded by NYSTEM

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Five projects led by researchers at the Columbia University Vagelos College of Physicians and Surgeons have been funded by the New York State Stem Cell Science program (NYSTEM) through Investigator Initiated Research Projects and Innovative, Developmental or Exploratory Activities in Stem Cell Research grants. NYSTEM is a $600 million program launched in 2007 to support stem cell research across New York state.

Dieter Egli , PhD, assistant professor of developmental cell biology (in pediatrics and obstetrics & gynecology) and Columbia Stem Cell Initiative (CSCI) member, is leading a two-year project deriving haploid human pluripotent stem cells from a single sperm. His work is aimed at understanding the functional significance of human genetic variation in health and disease.

Gordana Vunjak-Novakovic , PhD, University Professor, the Mikati Foundation Professor of Biomedical Engineering, professor of medical sciences, and a founding member of the CSCI, is leading a three-year project to study emergent cardiac behaviors by implementation of optical control of human cardiac tissues grown from optogenetic lines of cardiomyocytes from healthy individuals and patients with heart conditions causing arrhythmia. Her studies have implications for the management of arrhythmias in the human heart.

Hynek Wichterle , PhD, associate professor of pathology & cell biology, rehabilitation & regenerative medicine, and neuroscience (in neurology)  and CSCI member, and Kevin Kanning , PhD, assistant professor of pathology & cell biology at CUIMC, are leading a two-year project investigating transcriptional and chromatin regulators of motor neuron differentiation from embryonic stem cells. The team is developing a CRISPR-based screening platform that will enable powerful genetic access to motor neuron biology, identify novel modifiers of motor neuron specification, and provide an adaptable roadmap and tool set for the study of embryonic stem cell differentiation into other cell types.  

David Owens , PhD, associate professor of epithelial cell biology (in dermatology, pathology & cell biology, and dental medicine), is leading a three-year project investigating the cellular and molecular regulation of age-related loss of tactile acuity. His work could unlock how skin stem cells maintain a differentiated lineage of sensory cells that perceive light touch responses and how this process is perturbed with aging.  

Stephen Tsang , MD, PhD, the Laszlo T. Bito Associate Professor of Ophthalmology, associate professor of pathology & cell biology, and CSCI member, is leading a three-year project investigating treatments for juvenile macular degeneration at the Jonas Children’s Vision Care, New York-Presbyterian Hospital. His study could provide new innovative treatments for devastating ocular diseases affecting children.

Learning how scientists work: experiential research projects to promote cell biology learning and scientific process skills

Affiliation.

• 1 Department of Biology, Lake Forest College, Lake Forest, Illinois 60045, USA. [email protected]
• PMID: 12669101
• PMCID: PMC149805
• DOI: 10.1187/cbe.02-07-0024

Facilitating not only the mastery of sophisticated subject matter, but also the development of process skills is an ongoing challenge in teaching any introductory undergraduate course. To accomplish this goal in a sophomore-level introductory cell biology course, I require students to work in groups and complete several mock experiential research projects that imitate the professional activities of the scientific community. I designed these projects as a way to promote process skill development within content-rich pedagogy and to connect text-based and laboratory-based learning with the world of contemporary research. First, students become familiar with one primary article from a leading peer-reviewed journal, which they discuss by means of PowerPoint-based journal clubs and journalism reports highlighting public relevance. Second, relying mostly on primary articles, they investigate the molecular basis of a disease, compose reviews for an in-house journal, and present seminars in a public symposium. Last, students author primary articles detailing investigative experiments conducted in the lab. This curriculum has been successful in both quarter-based and semester-based institutions. Student attitudes toward their learning were assessed quantitatively with course surveys. Students consistently reported that these projects significantly lowered barriers to primary literature, improved research-associated skills, strengthened traditional pedagogy, and helped accomplish course objectives. Such approaches are widely suited for instructors seeking to integrate process with content in their courses.

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• v.1; Winter 2002

Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology

Robin wright.

* Department of Zoology, University of Washington, Seattle, Washington 98195

James Boggs

† Department of Communications, University of Washington, Seattle, Washington 98195

To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular and molecular biology of the disease, and recent research focused on understanding the cellular mechanisms of the disease process. To support effective teamwork and to help students develop collaboration skills useful for their future careers, we provide training in working in small groups. A final poster presentation, held in a public forum, summarizes what students have learned throughout the quarter. Although student satisfaction with the course is similar to that of standard lecture-based classes, a project-based class offers unique benefits to both the student and the instructor.

INTRODUCTION

A major challenge in teaching and learning cell biology is the enormous and continually expanding information base in our discipline. In just the year 2001, the National Libraries of Medicine PubMed database listed 136,775 articles with the word cell in their title or abstract. Nearly 6,300 articles published in 2001 contain the phrase “cell biology” or “cellular biology.” This increasing wealth of information makes designing a series of courses that “covers” all aspects of cell biology virtually impossible during the 4–5 yr that an undergraduate student spends at the university. The challenge is even more acute for universities such as the University of Washington, where most students take a single 10-week class in cell biology without any required laboratory section.

Students at the University of Washington can obtain Bachelor of Science degrees in cellular and molecular biology, ecology, evolution, and conservation biology, botany, zoology, neurobiology, microbiology, or biochemistry. Several cell biology courses are offered, including an introductory class (Introduction to Molecular Cell Biology, Biology 355) and two upper-division courses (Cell Biology, Biology 401; Molecular and Cellular Biology of Plants, Botany 428). None of these classes is required for completion of any of the biological sciences majors, but the 400-level cell biology courses are electives for all the degree programs. In addition, many cellular and molecular biology majors choose to take Biology 401 and a two-quarter biochemistry series in lieu of three quarters of biochemistry. (A significant overlap exists between the content of Biology 401 and the third quarter of a year-long biochemistry series, Biochemistry 442.) About 75% of the molecular and cellular biology majors take Biology 401 during their undergraduate education at the University of Washington. Students entering Biology 401 have taken 1 yr of general biology, which includes approximately 15 weeks of instruction in cell biology, genetics, and physiology. Students also must have completed at least two quarters of organic chemistry and either introductory cell biology or an upper-division class in genetics, physiology, or biochemistry. Thus, students enter Biology 401 with considerable experience in traditional, content-driven courses that cover material relevant to cell biology.

Biology 401 is a 5-credit course, representing approximately one-third of an average student's 15-credit-hour-per-quarter course load. The traditional, lecture-based course meets four times each week in three 50-min lectures and one 2-h, teaching assistant (TA)–led discussion section during which students analyze portions of research papers (see http://www.washington.edu/students/icd/S/biology/401mbhille.html ). Assessment of student performance is based on writing assignments, exams, and discussion-section participation. This traditional course design emphasizes learning key areas of cell biology content, as well as experimental methodology and analysis. Student evaluations at the end of the class indicate that they are well satisfied with the course (see http://www.google.com/u/washington?q=biol+401&hq=inurl%3Awww.washington.edu%2Fcec ).

After several years of teaching a traditional version of the upper-division cell biology course, I became concerned that students were not learning how to learn cell biology. My emphasis on content encouraged them to learn a lot of facts and figures but did not foster a true mastery of the skills that would be important for life after college, much less for graduate school or for professional careers in teaching or biomedical fields. As a result, I designed a new course that replaced essentially all faculty-delivered lectures with student-led team projects on the cellular and molecular biology of specific human diseases. This course redesign has proven to be successful in helping students learn how to navigate the complexity and volume of knowledge in cell biology, as well as to gain insight and appreciation for cell biology research. In addition, because I have much more substantive interactions with my students, the course has renewed my own delight in and commitment to teaching.

LOGISTICS OF THE PROJECT-BASED CELL BIOLOGY COURSE

General course format.

As shown in the syllabus (see Appendix A ), the revised class meets three times per week for 2 h. The 2-h class period is important for providing a sufficiently large block of time for students to make progress on their projects and helps in scheduling team presentations. After experimenting with other daily schedules, I determined that holding class meetings on three consecutive days (e.g., Tuesdays, Wednesdays, and Thursdays) is ideal. This schedule usually eliminates missed class periods because of holidays, and the clustering helps students schedule their work hours and other commitments. This schedule also provides research-active instructors with larger blocks of time to focus on their own research.

The class period is used for occasional lectures, classwide discussions, team meetings, team project presentations, and evaluation reviews. The occasional lectures are given as the need arises to share information with the entire class. For example, I usually give a 20-min sample talk on a novel disease to serve as an example for the second presentation. In addition, I often give an informal lecture on broadly relevant research methods such as immunoblotting and cloning techniques. We also discuss effective writing strategies, slide design, and ways to make an effective poster, using examples from my lab and from previous classes. However, on most days no formal presentation is scheduled. Instead, students are allowed to leave the classroom as necessary to work on computers or in the library. The instructor and a graduate TA are available in the classroom to discuss any issue related to content, experiments, presentation skills, or writing. The instructor and the TA also frequently go to the nearby computer facility to discuss the project as students work. Project presentations occur during the 2nd, 5th, 9th, and 10th weeks of class.

Students are required to purchase an appropriate cell biology textbook, such as Molecular Biology of the Cell ( Alberts et al ., 2002 ). The class is also given a list of the key cell biology research and review journals that are likely to be most useful in this class. Each team, in consultation with the instructor, identifies and assigns to the rest of the class appropriate textbook readings concerning their topic. For the second and third presentations, students are given instructor-chosen review articles and primary research articles as foundations on which to base their research and presentations. Students obtain from the library and the Internet additional information that is necessary to complete their projects. In early classes, a course web site was maintained that featured instructor-chosen information resources. However, this practice was discontinued because most of our current students are extremely skillful in doing Internet searches and did not find the class web site particularly useful. In addition, this resource did not promote the student's responsibility for and skill in obtaining and evaluating resources. Thus, instead of providing our own lists of relevant resources, we devote considerable class time to discussion of information literacy issues, including how to evaluate a potential source's reliability, and students are expected to find additional information on their own.

Four to five students work together as a team to research, prepare, and present both oral and written reports concerning the cell biology of a particular human disease. Depending on student input, the teams either focus on the same disease throughout the quarter or switch midway through the quarter. Student preferences are usually about equal on the matter of maintaining versus switching topics, and they realize the breadth versus depth trade-offs inherent in this decision.

The overall course is divided into four segments. The first three are punctuated with a paper and an oral presentation: the first segment focuses on the organelle or cellular process affected by the disease; the second segment deals with the cellular and molecular biology of the disease; the third segment focuses on recent research, with topics ranging from disease pathology to development of therapies to use of model organisms. The final segment is a poster presentation that allows students to bring all the information together into a coherent whole and serves as an impressively visible metric of how far they have come in their understanding and mastery of complicated information. The logic of this progression from simple to complex mirrors how most researchers, as experienced learners, approach new material. When confronted with a need to learn something completely new, we often begin with textbooks, move into review articles, and finally dig into the primary research.

Team Evaluation

At the beginning of each project segment, students receive an evaluation checklist that also serves as the grading standard for that project (see Appendixes B – D and Table ​ Table1). 1 ). Separate grades are given for the oral presentation and the paper. Evaluation of the work is explained in detail in a conference with the team, during which the focus is on what needs to be done to improve the quality of the presentation and paper. During this conference, we also ask questions about how the team is functioning and make suggestions for solving perceived problems with the process. After receiving this feedback (see Appendix A , Section IX, for an example) and that of the rest of the class, teams are usually allowed to rewrite their paper for a new grade.

Evaluation criteria and checklist of poster

Individual Evaluation

Full credit is earned by all team members who adequately contribute to the team project. The paper contains information about each student's individual contributions, including which student was the primary author of each section. In addition, the team maintains a project log that details each team meeting, who was in attendance, and what was accomplished (Table ​ (Table2). 2 ). Finally, each team member completes a confidential evaluation of the contributions of all other team members (Table ​ (Table3). 3 ). This information is typed up by the instructor to provide individual feedback (see Appendix A , Section X, for examples). By examining individual evaluations, the project log, the paper, and the individual portion of the presentation, the instructor can accurately evaluate whether each team member deserves full participation credit.

Example of a team project log a

Student names have been changed to protect privacy.

Team members' feedback forms

Initially, I was concerned about achieving fairness and accuracy in assigning appropriate grades to individuals that reflected both the quality of the group's work and an individual's contribution to that work. However, this system of checks and balances, together with the detailed conference with the team after each class segment, enables a substantive evaluation of student performance that is of potentially higher quality than that possible with traditional written exams. For example, the written documentation about the team process (log, individual evaluations, etc.) flags problems with equality of effort. These problems are discussed in the team conference, and members who did not contribute equally are given a decreased portion of the points earned. For instance, during the conference I may suggest that a particular individual appears to have contributed only 80% as much effort as that of the other team members. Often, the individual and his or her teammates admit the accuracy of the evaluation, and I assign the individual 80% of the total points earned by the team. Alternatively, the team members may explain the individual's contributions more accurately and that person earns full credit. Thus far, none of the end-of-quarter evaluations have revealed a concern by students that someone received a grade that he or she did not earn, which affirms that my assessment of an individual's grade is perceived to be fair and accurate.

In the week following a presentation, the instructor meets with each team to review the grading, highlight the positive aspects of the presentation and paper, and point out areas for improvement. Each student receives a written synopsis of this critique, together with a typewritten summary of colleagues' evaluations of their contributions (see Appendix A ).

Broadening of Learning and Individual Accountability

The philosophy of this class emphasizes group responsibility in contrast to that of the individual. Because the nature of modern biology also emphasizes group responsibility, as evidenced by the primacy of multiauthored papers, this emphasis is a valid representation of the current status of the cell biology discipline. However, as a way to encourage and evaluate each student's individual mastery of his or her topic as well as the topics of the other teams, one or two take-home exams or individual projects are assigned during the quarter. These exams or projects provide opportunities to promote greater breadth of learning and emphasize the importance of learning from one another. A sample assignment is to prepare a paper that compares and contrasts the molecular mechanisms of each disease presented in class.

The size of the class is limited by the number of student presentations that can be effectively given within two class periods. The second and third presentations (cellular and molecular biology of the disease and recent research) require 30-min time slots: 20 min for the talk, 5–8 min for questions, and a few minutes to change to the next team. Consequently, a single class section that meets in 2-h blocks can include as many as 40 students (eight teams of 5 students). A class with more than 40 students would need to be broken into multiple sections, each with 40 or fewer students. The major factor determining the smallest class size for a team-based approach is the need to have a sufficient number of projects so that students are exposed to a breadth and variety of cell biological information. I estimate that a minimum of six projects is required to meet this breadth goal. Thus, the smallest class size that would function well in this team-based framework would be 18 (six teams of 3 students). In my experience, smaller groups do not function as effectively in building teamwork skills. However, if the teamwork aspect of the course is not a priority, the class could contain as few as 6 students, each working independently.

SELECTION OF DISEASES FOR THE PROJECT-BASED CELL BIOLOGY COURSE

Two major criteria drive the choice of a particular disease for inclusion as a topic for learning cell biology. First, a recent research paper concerning a cell biologically relevant aspect of the disease must be available. Consequently, selection of the specific diseases to use in a particular quarter begins with searches for one to three recent research papers that use a variety of experimental approaches relevant to cell biology. The second criterion for choosing a particular disease is to provide a balance of topics so that the class will be introduced to a broad spectrum of cell biological subjects. For example, I typically try to select a spectrum of diseases that, when considered together, represent most major organelles within eukaryotic cells.

Although partial understanding of the underlying pathology of most of the selected diseases is not essential, it is helpful. A balance of “we don't yet know” opportunities along with diseases whose molecular bases have been well deciphered seems to work best for the class as a whole. Appendix E lists the diseases that were chosen during the past 2 yr, along with references to assigned review and research papers.

PROMOTION OF EFFECTIVE TEAMWORK

The challenge of change.

Probably the most frightening aspect of switching from lecture-based teaching to a project-based class is the challenge of making sure that teams work together effectively. Devoting most class periods to teamwork helps, because scheduling a time at which all team members can meet outside scheduled class periods is frequently impossible. However, simply having time to work together does not ensure that individuals within a team can actually work together effectively. To this end, the initial organizing of teams on the first day of class represents a critical nexus on which the success of the entire class rests. We devote most of the first 2-h class period to dividing students into teams and discussing how to work well in groups. Use of a “guild system,” as developed by Dr. James Boggs, has proven extremely effective for promoting effective teamwork and setting the stage for students to learn how to interact cooperatively. Additional suggestions for effective team building in undergraduate biology classes are given by Allen and Duch (1998) .

The Guild Concept

Before establishing teams, we divide the class into groups, or “guilds,” on the basis of each student's perception of his or her individual strengths. Four guilds seem to work well in building teams: 1) an administrator guild that organizes team efforts, 2) an artist guild that helps the team think creatively, 3) a communicator guild that facilitates interpersonal interactions among team members, and 4) an expeditor guild that steps in and performs functions as needed. After guilds are established, project teams are formed with individuals who represent each guild. Typically, each team includes only one individual from the administrative guild, but it can have multiple representatives from any of the other guilds.

The First Day of Class

After reviewing the syllabus, grading criteria, adds and drops, and other straightforward logistical issues related to the class, we begin by having each person tell us a positive adjective that describes one of his or her major strengths or “gifts.” One way to help students think about this adjective is to ask them to tell us how their friends would describe them. After a few minutes, the instructor asks each student to share this adjective or phrase with the rest of the class.

One by one, each student gives a descriptive adjective, which the instructor writes on the board without comment so that the adjectives are grouped into appropriate sets. For example, “organized” would be written on an unlabeled section of the board reserved for people who will become members of the administrator guild. “Creative” would be written on the area of the board reserved for the artist guild. “Flexible” would be written on an area of the board reserved for the expeditor guild. “Friendly” would be written on an area of the board reserved for the communicator guild. Characteristics appropriate for each guild are listed in Table ​ Table4. 4 . The instructor keeps tabs on only the administrator guild types and works to ensure that the number of administrators equals the eventual number of teams. If enough administrators have been found, the instructor asks the student to provide a second adjective and writes that word instead of the one that was first offered. Because everyone has multiple strengths, this shuffling of individuals into other groups is not viewed negatively, especially because the purpose of the grouping has not yet been revealed to the students.

Sample personal strength descriptors grouped into guilds

The students move so that they are sitting in groups as listed on the board and work together to select a guild name and motto. The students then discuss the positive contributions that their strengths bring to effective teamwork. Then, so that each individual can recognize the ways in which his or her strengths, if taken too far or used inappropriately, can cause problems for teams, the groups are asked to discuss the negative aspects of the guild. For instance, if someone in the administrator guild is “determined,” he or she may drive the others too hard and cause discord in the group.

After the guilds explore their strengths and weaknesses, the whole class reconvenes to discuss the positive and negative contributions of their guild members to effective teamwork. The class examines each guild's perspectives of its roles in team efforts and spends some time talking about the advantages and challenges of working together. Finally, teams are formed with one individual from the administrator guild and the remaining members from each of the other guilds. On the basis of experimenting for 4 yr with larger and smaller team sizes, I settled on having teams with four or five members as being ideal for spreading the work out equally and for buffering personality conflicts.

After introducing themselves to one another and spending time obtaining contact information, the teams are immediately set to work. They select a number from a hat and receive a corresponding folder that contains a story about an individual with the disease that they will be researching for the quarter. References to the identity of the disease have been removed from the story, but students are told that the disease is caused by a single genetic defect. They are asked to work together to devise a hypothesis to explain what cellular structure or process is altered as a result of the mutation.

The Structuring of Team Efforts

The initial three to four class periods are structured so that the teams must work together to complete specific tasks, such as learning how to do BLAST (Basic Local Alignment Search Tool) searches to identify their gene of interest. As the quarter progresses, direction from the instructor is gradually reduced to the point that the team does all planning for upcoming events. Appendix F provides an example of a structured activity that helps the teams learn how to plan and organize their projects.

Guild Meetings

Teams work together for several class periods, then a short guild meeting is called in which guild members can discuss what is working well in their groups, what problems are arising, and which ways they can effect positive change in their team. Such meetings are more important in the early weeks of the class (i.e., just before and after the first presentation) than later in the class. Teams seem to rapidly settle into a clear understanding and appreciation of each person's role and move forward with the tasks at hand. In addition, students learn to take on multiple roles as their talents and interests allow. Thus, the most important gains provided by the guild exercise may be in forming more “balanced” teams and in helping students realize, appreciate, and respect their teammates' abilities and contributions.

VALUE OF THE PROJECT-BASED CELL BIOLOGY CLASS

More than 60% of all students who enter the University of Washington think that what they will learn in their major will be “extremely important” for their success after leaving college. 1 However, when our students are surveyed 5–10 yr after graduation, only slightly more than 25% of the students find that what they learned in their major is “essential” for their current primary activity. 2 In contrast, the perceived importance of skills such as communication, problem solving, leadership, and working together effectively increases. Not surprisingly, students believe that their university training does a good job “teaching them their major” but not as well in helping them gain the skills that they tell us are important for success after college. The unfortunate conclusion is that we are doing a good job teaching our students things that may not matter much in the long run. The desire to make a long-term difference in students' lives and careers was one factor that motivated our developing a project-based cell biology class.

Project-based cell biology moves the students away from a focus on content to a clearly defined focus on communication, leadership, teamwork, and other skills needed for lifelong success, while modeling how scientists in general, and cell biologists in particular, learn new material. Although many students act as if they have been waiting all their lives to be allowed to tackle a problem creatively, others students are less comfortable with such open-ended activities ( Hansen and Stephens, 2000 ). As a consequence, my course evaluation scores remain essentially the same whether I teach a traditional lecture-based cell biology course or a completely project-based course. The student-perceived “effectiveness of the instructor” is usually decreased for the project-based course, probably because I am facilitating their independent learning rather than lecturing.

The most common criticism from students in the project-based course is that they think they did not learn as much as they would have in a lecture-based class. I believe that part of this dissatisfaction is an illusion; students appear to base their perception of the amount that they learned on the number of pages of lecture notes that they accumulate or the number of chapters that they were assigned to read. Student satisfaction with problem-based cell biology increased when I began handing out all the team articles and project papers and asking students to search for connections between their disease, organelle, process, and so forth, and those presented by the other teams ( Appendix G ). The amount of information we were “covering” became obvious as their notebooks filled with the presentation notes and papers from each team, as well as the entire complement of review and research articles for all the class projects.

An initial concern of many students confronting a project-based course for the first time stems from the requirement that they work in groups. Some students worry that their grades will suffer or that other team members will not work as hard and they will consequently receive a grade that they do not deserve. The underlying concern appears to be one of fairness. The integrated system of checks and balances (project logs, confidential team member evaluation, etc.) helps assure students that grading will be fair and take into account individual contributions. End-of-quarter evaluations confirm that the students perceive the grading to be fair, which indicates that these initial fears were unfounded. To deal with perceptions that an individual effort would be of higher quality than a group effort, I occasionally allow an individual to turn in a paper that represents his or her exclusive effort. With only one exception thus far, individual efforts are of poorer quality and receive lower grades than those of the corresponding team efforts. Once students see this result, they quickly become converts to the team approach.

In assessing course effectiveness, an initial issue is the student composition in the traditional classes versus that in the project-based class. Because the traditional classes are offered during the academic year and the project-based class is offered in the summer, the two types of classes may serve different populations of students. Comparisons of the summer 2000 class (project based) and the autumn 2000 class (traditional) uncovered two interesting differences: on average, students taking the project-based class had less than half as many transfer credits as those taking the traditional class, and the summer class contained four nonmatriculated students. Nonmatriculated students are rarely included in the academic-year Biology 401 classes because of high demand for the class by matriculated students. Despite these differences, both classes appear to include students with similar academic potential. For example, both classes have similar overall grade point averages (3.1 for the summer 2000 class [project based] and 3.2 for the autumn 2000 class). In addition, both classes have similar graduation rates: 83% of the summer 2000 class (project based) and 85% of the autumn 2000 class had obtained a biology degree by spring 2002. Most students in both classes are molecular and cellular biology majors.

Direct comparisons of student performance following lecture-based versus project-based courses are difficult or impossible because the two courses have different learning objectives and outcomes. However, one measurement of the effectiveness of project-based learning is evaluation of student performance at the beginning and at the end of the quarter. In the summer 2001 class, the average grade for the first project presentation was a “B” and the average paper grade was a “D.” By the second project, the average presentation grade improved to a solid and impressive “A,” a gain that was maintained in the final presentation, which also was “A”-quality work. The average paper grade on the second project improved to a “B+” and was an “A” for the third project. The rapidly improving and generally high grades in the project-based class demonstrate the ability of students working in teams to meet and often exceed even very high expectations.

Because of the nontraditional focus and format of the project-based cell biology class, one concern is that it may not prepare a student for subsequent traditional biology classes as well as a lecture-based cell biology class does. We do not have access to students' graduate record examinations (GRE) or Medical College Admission Test (MCAT) scores. Consequently, to assess this possibility, we compared the grades of the students taking Biology 401 in summer 2000 (project-based class) with those of the students taking Biology 401 in autumn 2000 (traditional class). The comparison, shown in Table ​ Table5, 5 , indicates that students taking the project-based class and those taking the traditional class had similar grades in subsequent biology classes. Thus, taking the project-based class did not adversely affect student performance in subsequent classes.

Comparison of biology grades of students before and after taking upper-division cell biology (Biology 401)

Summer 2000 class.

Fall 2000 class.

Standard deviation included when 20 or more data points were available.

Perhaps as important as the students' improved performance during the quarter and their overall satisfaction with the course (see Appendix H ) is that teaching a project-based class energizes me as a teacher and as an individual. I have learned new skills and approaches by watching how my students interact with one another. For example, one team struggled with an unusual team member, to the point that I offered them the option of essentially “voting the person off the island.” The team refused and, through their gentle but persistent efforts, was able to develop strategies for interacting with the recalcitrant individual, which enabled this person to contribute in substantial and novel ways to the team's efforts. Seeing such dedication in my students inspires me to greater efforts to teach all my classes in a way that is inclusive and more understanding of different learning styles, personalities, perspectives, strengths, and weaknesses.

Some of my students have been incredibly creative in ways that I would never have had the opportunity to see if I had not relinquished “control” of the class. For example, one team got in touch with a local epidermolysis bullosa (EB) support group and became acquainted with a young man who had this disease. They invited this young man to talk to the class about what it was like to live with EB. I have rarely seen a class as engaged, actually riveted, as when this young man talked about the traumas of being ridiculed when he was in elementary and high school for having to sit out of physical education classes or wear shoes several sizes too large. This engagement translates itself into a wonderful and welcome benefit: I have never heard a single student in my class ask, “Do I need to know this?” or “Is this going to be on the exam?” Life is the exam, and my students tell me that their experiences in our project-based class help prepare them for future academic and personal challenges.

Syllabus for Project-Based Cell Biology Class (Summer 2001)

I. class meetings, ii. instructors, iii. course goals.

The major goals of this class are to help you learn to:

• Ask questions about cell structure and function
• Understand how these questions can be addressed using modern research tools in cell biology
• Gain insight into the relevance of cell biological research to modern biology and medical science

These goals will be accomplished through completion of four team projects centered on discovering, understanding, and presenting the cellular and molecular biology of a human genetic disease. By the end of the quarter, you will be reading primary research papers and be able to explain the hypothesis, experimental approaches, methodology, controls, results, and shortcomings of the particular research.

IV. Course Philosophy

General: This course is designed to serve as a transition from lecture-based learning to inquiry-based learning, forming a bridge from your undergraduate classes to postgraduate or professional education. Most, if not all, courses that you have taken so far are designed to provide you with a survey of information about a particular topic. Instead, this course will help you learn to think like a scientist . Consequently, instead of sitting through lectures, you will work in a team to solve problems and give presentations to the rest of the class.

Thus, you will be directly responsible in large part for the success or failure of the course .

This responsibility means that you will probably need to work harder to be successful in this class than you have done in more traditional courses. We estimate that you will need to spend 10–15 hours per week studying outside of class time .

Cooperative learning: Throughout the course, you will be required to work in teams in order to complete several projects or to formulate presentations for class. Much of the lecture time will be spent working in these teams or presenting projects.

Instructors' responsibility: In this course, our job is to serve as expert learners who can help direct your explorations into the inner secrets of cells. Because the field of cell biology is so immense, we will be there to help keep you grounded and to point out the forest among the trees when you are in danger of getting lost in the details. We will offer suggestions, advice, and exhortation to help you achieve the maximum possible from this course. We will arrange for you to come to our lab or those of colleagues to see the techniques you need to understand for your presentation. We are partners with you in your learning—eager to help you find, evaluate, and use information or other resources that you need.

V. Logistics

The class is divided broadly into four major sections, each punctuated by a presentation in which your team shares what it has learned with the rest of the class and prepares a paper describing those results. The sections are:

• What is the structure and function of the cellular organelle or process in which this gene product works?
• What is the cellular and molecular biology of the disease caused by defects in this gene product?
• What experimental approaches are scientists taking to understand, treat, and/or cure this disease?
• Poster Presentation (summarizes all of the work you did).

In addition, the final week will be spent working on an individual miniproject or take-home exam that you will prepare on your own.

VI. Evaluation & Grades

For this class, your grade will reflect the quality of your team's projects (both the in-class presentation and the report), and your contribution to the projects.

Projects: Every project must involve the efforts of every team member. On written reports, each member must contribute a portion of the paper and each member must proofread and edit all of the contributions of the other members. The final report must be signed by each team member to confirm that each person has had input into and approves the final version of the report. In addition, the report will specifically describe each member's contributions. Finally, the report must include a project log that includes the times the team met, who was present, and a brief description of what was accomplished.

We will give a grade for the team report that reflects both the presentation and the written report. A checklist for each project will be provided, so you will know in advance what my expectations are for that project. In addition, each student in the team will secretly evaluate the contributions and participation of the other members of the team.

Thus, your final grade on the project will reflect my evaluation of your performance as a team as well as the evaluation of your individual participation by your peers. You will get plenty of feedback to make sure that you can improve your reports and projects over the course of the quarter. See the end of the syllabus for examples.

VII. Grading Policies

The specific grading policies will be established in collaboration with the class. One possibility is shown below:

There is no curve in this class. Your grade is the grade you earn, regardless of the performance of your classmates. This means that collaborative efforts should pay off for everyone. The following grade scale will be used:

Grading Standards

VII. Tentative Schedule of Activities

IX. Sample Feedback for Team Project

X. Sample Feedback for Individuals

In addition to the grading for the overall project, each person will receive an evaluation that reflects comments from the team. These comments will be typed by me and are anonymous. The idea is to give you a venue for making helpful comments to your team without hurting feelings or potentially damaging any working relationship. Here is an example of such an evaluation:

Evaluation Criteria and Checklist for Presentation and Paper on Cell Structure and Function

Cell Structure/Function Presentation Checklist Presentation and Papers on Tuesday, July 3, 2001, 8:30–10:40

Evaluation Criteria and Checklist for Presentation and Paper on Cellular and Molecular Biology of Human Disease

Cellular Molecular Biology of Disease Presentation Checklist Presentation and Papers Wednesday, July 18–Thursday, July 19

Evaluation Criteria and Checklist for Presentation and Paper on Recent Research on the Cellular Biology of Human Disease

Current Research Presentation Checklist Presentation and Papers on Wednesday, August 8–Thursday, August 9

Diseases and References Used in Project-Based Cell Biology Class (2000–2001) a , b

Abbreviations: ALDP = X-linked adrenolcukodystrophy protein; OMIM = Online Mendelian Inheritance in Man (web site); ANCR = Angelman Syndrome Chromosomal Region; ER = endoplasmic reticulum; NOG = noggin.

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Example of Guided Activity to Help Teams Plan and Organize Their Efforts

Comparison Chart of Features of Human Diseases

Data are taken from anonymous course evaluation forms completed at the end of the summer 2001 quarter. Thirty students responded, but not all questions were answered by all students. For some questions, an individual may have reported more than one answer. In these cases, all of the answers were used. Examples of statements were randomly chosen from answers that contained complete thoughts rather just a “yes” or “no” answer.

I was initially excited at first with the idea of working in a team because I like working with a small group and thought that this would lighten the course work per person.

I did not like the format because I don't like depending on other people's performance for my own grade.

I didn't think it was as valuable as I do now. It concerned me a little about group work time that would be required—how that might work.

Liked it a lot; I enjoy teamwork to combine my ideas.

Initially I was a little worried since sometimes groups can be challenging and frustrating!

Part of me was stoked because there weren't any big tests, but another part of me was pissed because attendance affected my grade.

I liked it and I didn't like it. I liked it because I thought the class would be more interactive & I would learn more; I didn't like it because I didn't want my grade to depend on others' work.

I thought it was a relief!

I thought it would be interesting, but I was a little wary of working in groups because they can be hard to work with.

I liked the concept initially. It sounded great because it was unlike any other class I had taken here.

I was looking forward to it until we got our first presentation grade. At that moment, I wished we didn't work in group.

Now that the class is over, what do you think are advantages and disadvantages of learning and doing projects in teams?

The advantages are that people can compensate and cover for fellow teammates. Also, teams can brainstorm for really creative ideas and sometimes a person can research part of the project that interests him/her the most. The disadvantages are that there might be conflicting working styles and personalities. Furthermore, one would have to be willing to compromise on ideas regarding papers, presentations, etc.

Teamwork forces people to work a little harder so you don't let your team members down. The disadvantage would be, some members may skate by on the work of the more motivated members.

Advantages—you learn more, cover more ground than you could by yourself; something may be uninteresting to one but interesting to another in your team.

Presentation & how to write scientific paper was greate [sic] opportunity. Even the [sic] only one member of the group doesn't work seriously, all group member [sic] get worse.

Advantage: more people = more ideas and more knowledge; Disadvantage: hard to coordinate our schedules for meeting times.

It was a big weight off, since I wasn't responsible for everything. Also, I think the final outcomes were much more creative than I could have done myself.

I'm more apt to ask for and receive criticism of my own work in the context of a team. However, all projects take several times longer to complete. The projects, of course, are usually of better quality.

Advantages: Get more info & do projects faster and better; Disadvantages: some people care more & do a little more work & the teacher can't see that.

1 D.E. McGhee, University of Washington Entering Student Survey 2001, Item 16 http://www.washington.edu/oea/0203freq.pdf , last accessed March 17, 2002.

2 D.E. McGhee, Undergraduate Degree Recipients: Five and Ten Years After Graduation, Item 11, http://www.washington.edu/oea/0006t.pdf , last accessed March 17, 2002.

• Alberts B., Johnson A., Lewis J., Raff M., Roberts K., Walter P. Molecular Biology of the Cell. Vol. 34. Garland; New York: 2002. p. 1463. [ Google Scholar ]
• Allen D. E., Duch B. J. Thinking Toward Solutions: Problem-Based Learning Activities for General Biology. Harcourt Brace & Company; Orlando, FL: 1998. [ Google Scholar ]
• Hansen E. J., Stephens J. A. The ethics of learner-centered education. Change. 2000; 32 :40–47. [ Google Scholar ]

ONLINE RESOURCES FOR INFORMATION ABOUT HUMAN DISEASES

• Family Village : Excellent collection of links to support groups and foundations for specific diseases. http://www.familyvillage.wisc.edu/index.htmlx
• GeneCards : Useful organization of links to information about specific human genes. http://nciarray.nci.nih.gov/cards/
• GeneTests·GeneClinics : Resource for disease symptoms and clinical tests; you must complete a lengthy but free registration that is well worth the effort. http://www.geneclinics.org/
• OMIM: Online Mendelian Inheritance in Man : Extremely useful, technical summaries of symptoms of, history of, basis of, and research on human genetic diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

Innovative 111+ Biotechnology Project Ideas – [2024 Updated]

• Post author By admin
• February 3, 2024

In the exciting world of biotechnology, where discoveries are always changing what we know, hands-on projects are like doors to new ideas and adventures.

Biotechnology is like a mix of biology, technology, and engineering. It goes beyond the usual limits and is important in changing how we do things in farming, healthcare, the environment, and industry.

Starting biotechnology projects helps you be creative and understand how life works more thoroughly. Whether a student, researcher, or just interested, working on biotechnology projects is like an exciting adventure where you get to try things out, learn, and be part of the ongoing scientific progress.

In this blog, we will delve into a myriad of Biotechnology Project Ideas that transcend traditional boundaries, inspiring you to embark on a journey of discovery. From enhancing agricultural productivity to revolutionizing healthcare, mitigating environmental challenges, and innovating industrial processes.

 These ideas encapsulate the essence of biotechnological potential. So, let’s explore the realms of biotechnology and ignite the spark of innovation that can shape a brighter future.

Table of Contents

What is Biotechnology?

Biotechnology is like a mix of biology, technology, and engineering. It’s all about using living things, cells, and biological systems to create new and improved stuff that can be useful in different industries.

Biotechnology is useful in medicine, farming, taking care of the environment, and in industries. Scientists use methods like changing genes, studying tiny biological parts, and growing cells in labs to make medicines, boost crop growth, and clean up pollution.

Biotechnology is crucial in advancing scientific understanding and finding practical applications for improving our lives and the world around us.

Importance of Biotechnology in Today’s Life

The importance of biotechnology projects lies in their potential to revolutionize various fields and address pressing global challenges. Here are key aspects highlighting the significance of biotechnology projects.

Medical Advancements

Development of new therapies and drugs, including personalized medicine tailored to individual genetic profiles.

Advances in gene therapy for treating genetic disorders and chronic diseases.

Innovative diagnostic tools and techniques, improving early detection and treatment.

Agricultural Innovation

Creation of genetically modified crops for increased yield, improved nutritional content, and resistance to pests and diseases.

Precision agriculture uses biotechnology to optimize resource use, reduce environmental impact, and enhance food security.

Sustainable farming practices with the development of biopesticides and biofertilizers.

Environmental Conservation

Bioremediation projects clean up polluted environments by using microorganisms to degrade or remove contaminants.

Waste-to-energy technologies contribute to the generation of clean and sustainable energy.

Development of eco-friendly solutions such as biodegradable plastics and materials.

Industrial Applications

Improved efficiency in industrial processes through enzyme engineering and bioprocessing.

Development of biosensors for real-time monitoring and quality control in manufacturing.

Bio-based materials and bio-manufacturing, reducing reliance on non-renewable resources.

Economic Impact

Job creation and economic growth through the expansion of biotechnology-related industries.

Increased competitiveness and innovation in global markets.

The potential for new revenue streams and business opportunities.

Addressing Global Challenges

Solutions for feeding a growing population through crop productivity and food technology advancements.

Sustainable energy sources and technologies to mitigate the impact of climate change.

Innovative healthcare solutions to combat emerging diseases and improve overall public health.

Research and Education

Advancing scientific knowledge and understanding of biological systems.

Providing opportunities for interdisciplinary research and collaboration.

Educating and training the next generation of scientists and professionals in cutting-edge technologies.

Ethics and Social Responsibility

Ethical considerations in biotechnology projects ensure responsible and transparent practices.

Socially responsible biotechnological applications that consider the impact on communities and ecosystems.

NOTE : Also Read “ 60+ Brilliant EBP Nursing Project Ideas: From Idea to Impact “

Innovative Biotechnology Project Ideas in Agricultural 

• Precision Farming using IoT and Biotechnology
• Plant-Microbe Interactions for Enhanced Crop Growth
• Biofortification of Crops for Improved Nutritional Value
• Sustainable Pest Management through Genetic Engineering
• Development of Drought-Resistant Crops
• Biocontrol of Plant Pathogens using Antimicrobial Peptides
• Genetic Modification for Extended Shelf Life of Fruits and Vegetables
• Soil Microbial Community Analysis for Crop Health
• Development of Heat-Tolerant Crop Varieties
• Harnessing Endophytic Microbes for Crop Protection

Medical Biotechnology Projects

• CRISPR-Cas9 Gene Editing for Genetic Disorders
• Development of a Biosensor for Cancer Biomarkers
• Personalized Medicine through Genomic Profiling
• Engineering Microbes for Drug Delivery
• 3D Bioprinting of Human Organs
• Stem Cell Therapy for Neurodegenerative Diseases
• Vaccine Development Using Recombinant DNA Technology
• Development of Rapid Diagnostic Kits for Infectious Diseases
• CRISPR-Cas9 in Antiviral Therapies
• Biocompatible Implants for Tissue Regeneration

Environmental Biotechnology Projects

• Microbial Fuel Cells for Renewable Energy Generation
• Biodegradation of Plastics Using Enzymes
• Monitoring Water Quality with Algal Biosensors
• Mycoremediation of Heavy Metal Contaminated Soil
• Methane Biofiltration in Wastewater Treatment
• Phytoremediation for Soil Cleanup
• Biofiltration of Airborne Pollutants using Bacteria
• Aquaponics Systems for Sustainable Food Production
• Harnessing Algae for Carbon Capture
• Development of Biogenic Nanoparticles for Water Purification

Industrial Biotechnology Projects

• Enzyme Engineering for Industrial Processes
• Metabolic Engineering for Bio-based Chemicals
• Bioprocess Optimization for Antibiotic Production
• Development of Enzymatic Biofuel Cells
• Bacterial Cellulose Production for Sustainable Textiles
• Biosurfactant Production for Environmental Applications
• Bioproduction of Flavors and Fragrances
• Bio-based Plastics from Agricultural Waste
• Biocatalysis for Pharmaceutical Synthesis
• Integration of Biotechnology in Food Processing

Food and Nutrition Biotechnology Projects

• Fermentation Technology for Probiotic Foods
• Genetic Modification for Enhanced Nutrient Content in Crops
• Development of Functional Foods using Biotechnology
• Cultured Meat Production Using Cell Culture Techniques
• Enzyme-Assisted Brewing and Distillation
• Biotechnological Approaches to Reduce Food Allergens
• Rapid Detection of Foodborne Pathogens
• Biofortification of Staple Crops with Micronutrients
• Algal Biotechnology for Nutraceuticals
• Development of Low-Gluten or Gluten-Free Wheat Varieties

Bioinformatics and Computational Biotechnology Projects

• Computational Drug Discovery using Molecular Docking
• Analysis of Biological Networks for Disease Prediction
• Machine Learning Algorithms for Genomic Data Analysis
• Comparative Genomics of Extremophiles
• Virtual Screening for Enzyme Inhibitors
• Modeling Protein-Protein Interactions
• Development of a Biomedical Image Analysis Tool
• Predictive Modeling of Protein Folding
• Evolutionary Algorithms in Synthetic Biology
• Systems Biology Approaches for Disease Pathways

Nanobiotechnology Projects

• Nanoparticle-Based Drug Delivery Systems
• Nanosensors for Detection of Environmental Pollutants
• Gold Nanoparticles in Cancer Diagnosis and Therapy
• Nanobiomaterials for Tissue Engineering
• Quantum Dots in Biological Imaging
• Magnetic Nanoparticles for Hyperthermia Treatment
• Carbon Nanotubes for Drug Delivery Applications
• Nanotechnology in Crop Protection
• Nanoencapsulation of Bioactive Compounds in Food
• Liposomal Nanocarriers for Vaccine Delivery

Synthetic Biology Projects

• BioBrick Construction for Synthetic Biological Systems
• Design and Construction of Minimal Genomes
• Development of Programmable RNA Devices
• Synthetic Biology Approaches to Biofuel Production
• Genetic Circuits for Bioremediation Applications
• Optogenetic Control of Cellular Processes
• Directed Evolution of Enzymes for Specific Functions
• Synthetic Microbial Consortia for Industrial Applications
• CRISPR-Cas9-Based Synthetic Gene Circuits
• Biocontainment Strategies for Engineered Organisms

Stem Cell and Regenerative Medicine Projects

• Differentiation of Induced Pluripotent Stem Cells
• Biomaterials for Stem Cell Delivery in Regenerative Medicine
• Stem Cell-Based Therapies for Cardiovascular Diseases
• Biofabrication of Scaffold-Free Tissues
• Organoids as Models for Drug Testing
• Stem Cells in Wound Healing and Tissue Repair
• Engineering Artificial Organs for Transplantation
• 3D Bioprinting of Vascularized Tissues
• Stem Cells in Spinal Cord Injury Repair
• In vitro Models of Human Development Using Stem Cells

Biotechnology Ethics and Policy Projects

• Ethical Implications of CRISPR-Cas9 Technology
• Regulatory Frameworks for Genetically Modified Organisms
• Biosecurity in Biotechnology Research
• Access to Biotechnology in Developing Countries
• Public Perception of Genetically Modified Foods
• Intellectual Property Issues in Biotechnology
• Ethical Considerations in Human Gene Editing
• Environmental Impact Assessment of Biotechnological Processes
• Informed Consent in Biomedical Research
• Policies and Regulations for Biobanking

Marine Biotechnology Projects

• Bioprospecting for Novel Marine Microorganisms
• Algal Biotechnology for Biofuel Production
• Marine Enzymes in Industrial Applications
• Coral Microbiome Research for Conservation
• Marine Bioplastics from Algae
• Marine Natural Products for Drug Discovery
• Bioremediation of Oil Spills using Marine Microbes
• Marine Biotechnology for Aquaculture
• Metagenomics of Deep-Sea Environments
• Marine Bacterial Biofilms for Industrial Applications

Education and Outreach Projects

• Biotechnology Workshops for High School Students
• Creation of Educational Biotechnology Kits
• Virtual Laboratories for Biotechnology Learning
• Biotechnology Outreach Programs in Communities
• Development of Educational Games for Biotechnology
• Biotechnology Science Fairs and Competitions
• Online Biotechnology Courses for the Public
• Science Communication in Biotechnology
• Establishment of Biotechnology Learning Centers
• STEM Education Integration with Biotechnology

Biotechnology offers exciting project ideas for students and hobbyists of all levels. From simple at-home experiments with yeast and bacteria to more advanced projects in genetic engineering , there are biotech projects to interest and suit anyone. 

While proper safety measures, ethical thinking, and supervision should always be used, especially for young students, biotech projects allow for valuable hands-on learning about this fascinating and fast-growing area. Whether you want to design a new bacteria strain, mimic natural selection, or extract your DNA, biotechnology welcomes your curiosity and innovation. 

This article has outlined some key biotech project concepts and possibilities, showing how biotech provides impactful educational experiences. With so many options to actively explore science, consider starting your biotech journey today.

Why should I consider a biotechnology project?

Biotechnology projects offer opportunities to contribute to scientific advancements, address real-world problems, and positively impact society. They provide a platform for innovation and creativity.

How do I choose the right biotechnology project?

Consider factors such as relevance to current challenges, feasibility, potential impact, available resources, and personal interests. The blog provides criteria to help guide the selection process.

Are there specific areas within biotechnology that are more promising for projects?

The blog outlines different areas for biotechnology projects, including healthcare, agriculture, environmental conservation, and industrial applications. Each section provides project ideas in those respective domains.

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Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology

• Robin Wright
• James Boggs

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To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular and molecular biology of the disease, and recent research focused on understanding the cellular mechanisms of the disease process. To support effective teamwork and to help students develop collaboration skills useful for their future careers, we provide training in working in small groups. A final poster presentation, held in a public forum, summarizes what students have learned throughout the quarter. Although student satisfaction with the course is similar to that of standard lecture-based classes, a project-based class offers unique benefits to both the student and the instructor.

INTRODUCTION

A major challenge in teaching and learning cell biology is the enormous and continually expanding information base in our discipline. In just the year 2001, the National Libraries of Medicine PubMed database listed 136,775 articles with the word cell in their title or abstract. Nearly 6,300 articles published in 2001 contain the phrase “cell biology” or“ cellular biology.” This increasing wealth of information makes designing a series of courses that “covers” all aspects of cell biology virtually impossible during the 4-5 yr that an undergraduate student spends at the university. The challenge is even more acute for universities such as the University of Washington, where most students take a single 10-week class in cell biology without any required laboratory section.

Students at the University of Washington can obtain Bachelor of Science degrees in cellular and molecular biology, ecology, evolution, and conservation biology, botany, zoology, neurobiology, microbiology, or biochemistry. Several cell biology courses are offered, including an introductory class (Introduction to Molecular Cell Biology, Biology 355) and two upper-division courses (Cell Biology, Biology 401; Molecular and Cellular Biology of Plants, Botany 428). None of these classes is required for completion of any of the biological sciences majors, but the 400-level cell biology courses are electives for all the degree programs. In addition, many cellular and molecular biology majors choose to take Biology 401 and a two-quarter biochemistry series in lieu of three quarters of biochemistry. (A significant overlap exists between the content of Biology 401 and the third quarter of a year-long biochemistry series, Biochemistry 442.) About 75% of the molecular and cellular biology majors take Biology 401 during their undergraduate education at the University of Washington. Students entering Biology 401 have taken 1 yr of general biology, which includes approximately 15 weeks of instruction in cell biology, genetics, and physiology. Students also must have completed at least two quarters of organic chemistry and either introductory cell biology or an upper-division class in genetics, physiology, or biochemistry. Thus, students enter Biology 401 with considerable experience in traditional, content-driven courses that cover material relevant to cell biology.

Biology 401 is a 5-credit course, representing approximately one-third of an average student's 15-credit-hour-per-quarter course load. The traditional, lecture-based course meets four times each week in three 50-min lectures and one 2-h, teaching assistant (TA)-led discussion section during which students analyze portions of research papers (see http://www.washington.edu/students/icd/S/biology/401mbhille.html ). Assessment of student performance is based on writing assignments, exams, and discussion-section participation. This traditional course design emphasizes learning key areas of cell biology content, as well as experimental methodology and analysis. Student evaluations at the end of the class indicate that they are well satisfied with the course (see http://www.google.com/u/washington?q=biol+401&hq=inurl%3Awww.washington.edu%2Fcec ).

After several years of teaching a traditional version of the upper-division cell biology course, I became concerned that students were not learning how to learn cell biology. My emphasis on content encouraged them to learn a lot of facts and figures but did not foster a true mastery of the skills that would be important for life after college, much less for graduate school or for professional careers in teaching or biomedical fields. As a result, I designed a new course that replaced essentially all faculty-delivered lectures with student-led team projects on the cellular and molecular biology of specific human diseases. This course redesign has proven to be successful in helping students learn how to navigate the complexity and volume of knowledge in cell biology, as well as to gain insight and appreciation for cell biology research. In addition, because I have much more substantive interactions with my students, the course has renewed my own delight in and commitment to teaching.

LOGISTICS OF THE PROJECT-BASED CELL BIOLOGY COURSE

General course format.

As shown in the syllabus (see Appendix A ), the revised class meets three times per week for 2 h. The 2-h class period is important for providing a sufficiently large block of time for students to make progress on their projects and helps in scheduling team presentations. After experimenting with other daily schedules, I determined that holding class meetings on three consecutive days (e.g., Tuesdays, Wednesdays, and Thursdays) is ideal. This schedule usually eliminates missed class periods because of holidays, and the clustering helps students schedule their work hours and other commitments. This schedule also provides research-active instructors with larger blocks of time to focus on their own research.

The class period is used for occasional lectures, classwide discussions, team meetings, team project presentations, and evaluation reviews. The occasional lectures are given as the need arises to share information with the entire class. For example, I usually give a 20-min sample talk on a novel disease to serve as an example for the second presentation. In addition, I often give an informal lecture on broadly relevant research methods such as immunoblotting and cloning techniques. We also discuss effective writing strategies, slide design, and ways to make an effective poster, using examples from my lab and from previous classes. However, on most days no formal presentation is scheduled. Instead, students are allowed to leave the classroom as necessary to work on computers or in the library. The instructor and a graduate TA are available in the classroom to discuss any issue related to content, experiments, presentation skills, or writing. The instructor and the TA also frequently go to the nearby computer facility to discuss the project as students work. Project presentations occur during the 2nd, 5th, 9th, and 10th weeks of class.

Students are required to purchase an appropriate cell biology textbook, such as Molecular Biology of the Cell ( Alberts et al. , 2002 ). The class is also given a list of the key cell biology research and review journals that are likely to be most useful in this class. Each team, in consultation with the instructor, identifies and assigns to the rest of the class appropriate textbook readings concerning their topic. For the second and third presentations, students are given instructor-chosen review articles and primary research articles as foundations on which to base their research and presentations. Students obtain from the library and the Internet additional information that is necessary to complete their projects. In early classes, a course web site was maintained that featured instructor-chosen information resources. However, this practice was discontinued because most of our current students are extremely skillful in doing Internet searches and did not find the class web site particularly useful. In addition, this resource did not promote the student's responsibility for and skill in obtaining and evaluating resources. Thus, instead of providing our own lists of relevant resources, we devote considerable class time to discussion of information literacy issues, including how to evaluate a potential source's reliability, and students are expected to find additional information on their own.

Four to five students work together as a team to research, prepare, and present both oral and written reports concerning the cell biology of a particular human disease. Depending on student input, the teams either focus on the same disease throughout the quarter or switch midway through the quarter. Student preferences are usually about equal on the matter of maintaining versus switching topics, and they realize the breadth versus depth trade-offs inherent in this decision.

The overall course is divided into four segments. The first three are punctuated with a paper and an oral presentation: the first segment focuses on the organelle or cellular process affected by the disease; the second segment deals with the cellular and molecular biology of the disease; the third segment focuses on recent research, with topics ranging from disease pathology to development of therapies to use of model organisms. The final segment is a poster presentation that allows students to bring all the information together into a coherent whole and serves as an impressively visible metric of how far they have come in their understanding and mastery of complicated information. The logic of this progression from simple to complex mirrors how most researchers, as experienced learners, approach new material. When confronted with a need to learn something completely new, we often begin with textbooks, move into review articles, and finally dig into the primary research.

Team Evaluation

At the beginning of each project segment, students receive an evaluation checklist that also serves as the grading standard for that project (see Appendixes B ), C ), D ) and Table 1 ). Separate grades are given for the oral presentation and the paper. Evaluation of the work is explained in detail in a conference with the team, during which the focus is on what needs to be done to improve the quality of the presentation and paper. During this conference, we also ask questions about how the team is functioning and make suggestions for solving perceived problems with the process. After receiving this feedback (see Appendix A, Section IX , for an example) and that of the rest of the class, teams are usually allowed to rewrite their paper for a new grade.

Individual Evaluation

Full credit is earned by all team members who adequately contribute to the team project. The paper contains information about each student's individual contributions, including which student was the primary author of each section. In addition, the team maintains a project log that details each team meeting, who was in attendance, and what was accomplished ( Table 2 ). Finally, each team member completes a confidential evaluation of the contributions of all other team members ( Table 3 ). This information is typed up by the instructor to provide individual feedback (see Appendix A, Section X , for examples). By examining individual evaluations, the project log, the paper, and the individual portion of the presentation, the instructor can accurately evaluate whether each team member deserves full participation credit.

Initially, I was concerned about achieving fairness and accuracy in assigning appropriate grades to individuals that reflected both the quality of the group's work and an individual's contribution to that work. However, this system of checks and balances, together with the detailed conference with the team after each class segment, enables a substantive evaluation of student performance that is of potentially higher quality than that possible with traditional written exams. For example, the written documentation about the team process (log, individual evaluations, etc.) flags problems with equality of effort. These problems are discussed in the team conference, and members who did not contribute equally are given a decreased portion of the points earned. For instance, during the conference I may suggest that a particular individual appears to have contributed only 80% as much effort as that of the other team members. Often, the individual and his or her teammates admit the accuracy of the evaluation, and I assign the individual 80% of the total points earned by the team. Alternatively, the team members may explain the individual's contributions more accurately and that person earns full credit. Thus far, none of the end-of-quarter evaluations have revealed a concern by students that someone received a grade that he or she did not earn, which affirms that my assessment of an individual's grade is perceived to be fair and accurate.

In the week following a presentation, the instructor meets with each team to review the grading, highlight the positive aspects of the presentation and paper, and point out areas for improvement. Each student receives a written synopsis of this critique, together with a typewritten summary of colleagues' evaluations of their contributions (see Appendix A ).

Broadening of Learning and Individual Accountability

The philosophy of this class emphasizes group responsibility in contrast to that of the individual. Because the nature of modern biology also emphasizes group responsibility, as evidenced by the primacy of multiauthored papers, this emphasis is a valid representation of the current status of the cell biology discipline. However, as a way to encourage and evaluate each student's individual mastery of his or her topic as well as the topics of the other teams, one or two take-home exams or individual projects are assigned during the quarter. These exams or projects provide opportunities to promote greater breadth of learning and emphasize the importance of learning from one another. A sample assignment is to prepare a paper that compares and contrasts the molecular mechanisms of each disease presented in class.

The size of the class is limited by the number of student presentations that can be effectively given within two class periods. The second and third presentations (cellular and molecular biology of the disease and recent research) require 30-min time slots: 20 min for the talk, 5-8 min for questions, and a few minutes to change to the next team. Consequently, a single class section that meets in 2-h blocks can include as many as 40 students (eight teams of 5 students). A class with more than 40 students would need to be broken into multiple sections, each with 40 or fewer students. The major factor determining the smallest class size for a team-based approach is the need to have a sufficient number of projects so that students are exposed to a breadth and variety of cell biological information. I estimate that a minimum of six projects is required to meet this breadth goal. Thus, the smallest class size that would function well in this team-based framework would be 18 (six teams of 3 students). In my experience, smaller groups do not function as effectively in building teamwork skills. However, if the teamwork aspect of the course is not a priority, the class could contain as few as 6 students, each working independently.

SELECTION OF DISEASES FOR THE PROJECT-BASED CELL BIOLOGY COURSE

Two major criteria drive the choice of a particular disease for inclusion as a topic for learning cell biology. First, a recent research paper concerning a cell biologically relevant aspect of the disease must be available. Consequently, selection of the specific diseases to use in a particular quarter begins with searches for one to three recent research papers that use a variety of experimental approaches relevant to cell biology. The second criterion for choosing a particular disease is to provide a balance of topics so that the class will be introduced to a broad spectrum of cell biological subjects. For example, I typically try to select a spectrum of diseases that, when considered together, represent most major organelles within eukaryotic cells.

Although partial understanding of the underlying pathology of most of the selected diseases is not essential, it is helpful. A balance of “we don't yet know” opportunities along with diseases whose molecular bases have been well deciphered seems to work best for the class as a whole. Appendix E lists the diseases that were chosen during the past 2 yr, along with references to assigned review and research papers.

PROMOTION OF EFFECTIVE TEAMWORK

The challenge of change.

Probably the most frightening aspect of switching from lecture-based teaching to a project-based class is the challenge of making sure that teams work together effectively. Devoting most class periods to teamwork helps, because scheduling a time at which all team members can meet outside scheduled class periods is frequently impossible. However, simply having time to work together does not ensure that individuals within a team can actually work together effectively. To this end, the initial organizing of teams on the first day of class represents a critical nexus on which the success of the entire class rests. We devote most of the first 2-h class period to dividing students into teams and discussing how to work well in groups. Use of a“ guild system,” as developed by Dr. James Boggs, has proven extremely effective for promoting effective teamwork and setting the stage for students to learn how to interact cooperatively. Additional suggestions for effective team building in undergraduate biology classes are given by Allen and Duch ( 1998 ).

The Guild Concept

Before establishing teams, we divide the class into groups, or“ guilds,” on the basis of each student's perception of his or her individual strengths. Four guilds seem to work well in building teams: 1) an administrator guild that organizes team efforts, 2) an artist guild that helps the team think creatively, 3) a communicator guild that facilitates interpersonal interactions among team members, and 4) an expeditor guild that steps in and performs functions as needed. After guilds are established, project teams are formed with individuals who represent each guild. Typically, each team includes only one individual from the administrative guild, but it can have multiple representatives from any of the other guilds.

The First Day of Class

After reviewing the syllabus, grading criteria, adds and drops, and other straightforward logistical issues related to the class, we begin by having each person tell us a positive adjective that describes one of his or her major strengths or “gifts.” One way to help students think about this adjective is to ask them to tell us how their friends would describe them. After a few minutes, the instructor asks each student to share this adjective or phrase with the rest of the class.

One by one, each student gives a descriptive adjective, which the instructor writes on the board without comment so that the adjectives are grouped into appropriate sets. For example, “organized” would be written on an unlabeled section of the board reserved for people who will become members of the administrator guild. “Creative” would be written on the area of the board reserved for the artist guild.“ Flexible” would be written on an area of the board reserved for the expeditor guild. “Friendly” would be written on an area of the board reserved for the communicator guild. Characteristics appropriate for each guild are listed in Table 4 . The instructor keeps tabs on only the administrator guild types and works to ensure that the number of administrators equals the eventual number of teams. If enough administrators have been found, the instructor asks the student to provide a second adjective and writes that word instead of the one that was first offered. Because everyone has multiple strengths, this shuffling of individuals into other groups is not viewed negatively, especially because the purpose of the grouping has not yet been revealed to the students.

The students move so that they are sitting in groups as listed on the board and work together to select a guild name and motto. The students then discuss the positive contributions that their strengths bring to effective teamwork. Then, so that each individual can recognize the ways in which his or her strengths, if taken too far or used inappropriately, can cause problems for teams, the groups are asked to discuss the negative aspects of the guild. For instance, if someone in the administrator guild is “determined,” he or she may drive the others too hard and cause discord in the group.

After the guilds explore their strengths and weaknesses, the whole class reconvenes to discuss the positive and negative contributions of their guild members to effective teamwork. The class examines each guild's perspectives of its roles in team efforts and spends some time talking about the advantages and challenges of working together. Finally, teams are formed with one individual from the administrator guild and the remaining members from each of the other guilds. On the basis of experimenting for 4 yr with larger and smaller team sizes, I settled on having teams with four or five members as being ideal for spreading the work out equally and for buffering personality conflicts.

After introducing themselves to one another and spending time obtaining contact information, the teams are immediately set to work. They select a number from a hat and receive a corresponding folder that contains a story about an individual with the disease that they will be researching for the quarter. References to the identity of the disease have been removed from the story, but students are told that the disease is caused by a single genetic defect. They are asked to work together to devise a hypothesis to explain what cellular structure or process is altered as a result of the mutation.

The Structuring of Team Efforts

The initial three to four class periods are structured so that the teams must work together to complete specific tasks, such as learning how to do BLAST (Basic Local Alignment Search Tool) searches to identify their gene of interest. As the quarter progresses, direction from the instructor is gradually reduced to the point that the team does all planning for upcoming events. Appendix F provides an example of a structured activity that helps the teams learn how to plan and organize their projects.

Guild Meetings

Teams work together for several class periods, then a short guild meeting is called in which guild members can discuss what is working well in their groups, what problems are arising, and which ways they can effect positive change in their team. Such meetings are more important in the early weeks of the class (i.e., just before and after the first presentation) than later in the class. Teams seem to rapidly settle into a clear understanding and appreciation of each person's role and move forward with the tasks at hand. In addition, students learn to take on multiple roles as their talents and interests allow. Thus, the most important gains provided by the guild exercise may be in forming more “balanced” teams and in helping students realize, appreciate, and respect their teammates' abilities and contributions.

VALUE OF THE PROJECT-BASED CELL BIOLOGY CLASS

More than 60% of all students who enter the University of Washington think that what they will learn in their major will be “extremely important” for their success after leaving college. 1 However, when our students are surveyed 5-10 yr after graduation, only slightly more than 25% of the students find that what they learned in their major is“ essential” for their current primary activity. 2 In contrast, the perceived importance of skills such as communication, problem solving, leadership, and working together effectively increases. Not surprisingly, students believe that their university training does a good job“ teaching them their major” but not as well in helping them gain the skills that they tell us are important for success after college. The unfortunate conclusion is that we are doing a good job teaching our students things that may not matter much in the long run. The desire to make a longterm difference in students' lives and careers was one factor that motivated our developing a project-based cell biology class.

1D.E. McGhee, University of Washington Entering Student Survey 2001, Item 16, http://www.washington.edu/oea/0203freq.pdf , last accessed March 17, 2002.

2D.E. McGhee, Undergraduate Degree Recipients: Five and Ten Years After Graduation, Item 11, http://www.washington.edu/oea/0006t.pdf , last accessed March 17, 2002.

Project-based cell biology moves the students away from a focus on content to a clearly defined focus on communication, leadership, teamwork, and other skills needed for lifelong success, while modeling how scientists in general, and cell biologists in particular, learn new material. Although many students act as if they have been waiting all their lives to be allowed to tackle a problem creatively, others students are less comfortable with such open-ended activities ( Hansen and Stephens, 2000 ). As a consequence, my course evaluation scores remain essentially the same whether I teach a traditional lecture-based cell biology course or a completely project-based course. The student-perceived“ effectiveness of the instructor” is usually decreased for the project-based course, probably because I am facilitating their independent learning rather than lecturing.

The most common criticism from students in the project-based course is that they think they did not learn as much as they would have in a lecture-based class. I believe that part of this dissatisfaction is an illusion; students appear to base their perception of the amount that they learned on the number of pages of lecture notes that they accumulate or the number of chapters that they were assigned to read. Student satisfaction with problem-based cell biology increased when I began handing out all the team articles and project papers and asking students to search for connections between their disease, organelle, process, and so forth, and those presented by the other teams ( Appendix G ). The amount of information we were “covering” became obvious as their notebooks filled with the presentation notes and papers from each team, as well as the entire complement of review and research articles for all the class projects.

An initial concern of many students confronting a project-based course for the first time stems from the requirement that they work in groups. Some students worry that their grades will suffer or that other team members will not work as hard and they will consequently receive a grade that they do not deserve. The underlying concern appears to be one of fairness. The integrated system of checks and balances (project logs, confidential team member evaluation, etc.) helps assure students that grading will be fair and take into account individual contributions. End-of-quarter evaluations confirm that the students perceive the grading to be fair, which indicates that these initial fears were unfounded. To deal with perceptions that an individual effort would be of higher quality than a group effort, I occasionally allow an individual to turn in a paper that represents his or her exclusive effort. With only one exception thus far, individual efforts are of poorer quality and receive lower grades than those of the corresponding team efforts. Once students see this result, they quickly become converts to the team approach.

In assessing course effectiveness, an initial issue is the student composition in the traditional classes versus that in the project-based class. Because the traditional classes are offered during the academic year and the project-based class is offered in the summer, the two types of classes may serve different populations of students. Comparisons of the summer 2000 class (project based) and the autumn 2000 class (traditional) uncovered two interesting differences: on average, students taking the project-based class had less than half as many transfer credits as those taking the traditional class, and the summer class contained four nonmatriculated students. Nonmatriculated students are rarely included in the academic-year Biology 401 classes because of high demand for the class by matriculated students. Despite these differences, both classes appear to include students with similar academic potential. For example, both classes have similar overall grade point averages (3.1 for the summer 2000 class [project based] and 3.2 for the autumn 2000 class). In addition, both classes have similar graduation rates: 83% of the summer 2000 class (project based) and 85% of the autumn 2000 class had obtained a biology degree by spring 2002. Most students in both classes are molecular and cellular biology majors.

Direct comparisons of student performance following lecture-based versus project-based courses are difficult or impossible because the two courses have different learning objectives and outcomes. However, one measurement of the effectiveness of project-based learning is evaluation of student performance at the beginning and at the end of the quarter. In the summer 2001 class, the average grade for the first project presentation was a “B” and the average paper grade was a “D.” By the second project, the average presentation grade improved to a solid and impressive “A,” a gain that was maintained in the final presentation, which also was“ A”-quality work. The average paper grade on the second project improved to a “B+” and was an “A” for the third project. The rapidly improving and generally high grades in the project-based class demonstrate the ability of students working in teams to meet and often exceed even very high expectations.

Because of the nontraditional focus and format of the project-based cell biology class, one concern is that it may not prepare a student for subsequent traditional biology classes as well as a lecture-based cell biology class does. We do not have access to students' graduate record examinations (GRE) or Medical College Admission Test (MCAT) scores. Consequently, to assess this possibility, we compared the grades of the students taking Biology 401 in summer 2000 (project-based class) with those of the students taking Biology 401 in autumn 2000 (traditional class). The comparison, shown in Table 5 , indicates that students taking the project-based class and those taking the traditional class had similar grades in subsequent biology classes. Thus, taking the project-based class did not adversely affect student performance in subsequent classes.

a Summer 2000 class

b Fall 2000 class

c Standard deviation included when 20 or more data points were available

Perhaps as important as the students' improved performance during the quarter and their overall satisfaction with the course (see Appendix H ) is that teaching a project-based class energizes me as a teacher and as an individual. I have learned new skills and approaches by watching how my students interact with one another. For example, one team struggled with an unusual team member, to the point that I offered them the option of essentially “voting the person off the island.” The team refused and, through their gentle but persistent efforts, was able to develop strategies for interacting with the recalcitrant individual, which enabled this person to contribute in substantial and novel ways to the team's efforts. Seeing such dedication in my students inspires me to greater efforts to teach all my classes in a way that is inclusive and more understanding of different learning styles, personalities, perspectives, strengths, and weaknesses.

Some of my students have been incredibly creative in ways that I would never have had the opportunity to see if I had not relinquished“ control” of the class. For example, one team got in touch with a local epidermolysis bullosa (EB) support group and became acquainted with a young man who had this disease. They invited this young man to talk to the class about what it was like to live with EB. I have rarely seen a class as engaged, actually riveted, as when this young man talked about the traumas of being ridiculed when he was in elementary and high school for having to sit out of physical education classes or wear shoes several sizes too large. This engagement translates itself into a wonderful and welcome benefit: I have never heard a single student in my class ask, “Do I need to know this?” or “Is this going to be on the exam?” Life is the exam, and my students tell me that their experiences in our project-based class help prepare them for future academic and personal challenges.

ONLINE RESOURCES FOR INFORMATION ABOUT HUMAN DISEASES

Family Village : Excellent collection of links to support groups and foundations for specific diseases. http://www.familyvillage.wisc.edu/index.htmlx

GeneCards : Useful organization of links to information about specific human genes. http://nciarray.nci.nih.gov/cards/

GeneTests·GeneClinics : Resource for disease symptoms and clinical tests; you must complete a lengthy but free registration that is well worth the effort. http://www.geneclinics.org/

OMIM: Online Mendelian Inheritance in Man : Extremely useful, technical summaries of symptoms of, history of, basis of, and research on human genetic diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

Monitoring Editor: Elizabeth Vallen

• Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. ( 2002 ). Molecular Biology of the Cell , New York: Garland, xxxiv ,1463 . Google Scholar
• Allen, D.E., and Duch, B.J. ( 1998 ). Thinking Toward Solutions: Problem-Based Learning Activities for General Biology , Orlando, FL: Harcourt Brace & Company. Google Scholar
• Hansen, E.J., and Stephens, J.A. ( 2000 ). The ethics of learner-centered education. Change 32 , 40-47. Google Scholar
• Viking Spectrophotometer: A Home-Built, Simple, and Cost-Efficient Absorption and Fluorescence Spectrophotometer for Education in Chemistry 9 February 2023 | Journal of Chemical Education, Vol. 100, No. 3
• Storytelling as a Tool to Enhance Conceptual Knowledge in Cell Biology 12 July 2022 | Journal of Microbiology & Biology Education, Vol. 34
• A comprehensive framework and tool for supporting progressive learning of software development in an academic learning environment 20 September 2021 | Computer Applications in Engineering Education, Vol. 30, No. 2
• Applications of microscopy in science education: gifted youth, public school, and the next-generation science standards (NGSS) 28 January 2020 | Journal of Biological Education, Vol. 55, No. 5
• Trying to do it all in a single course: a surprisingly good idea
• Student Motivation from and Resistance to Active Learning Rooted in Essential Science Practices 23 December 2017 | Research in Science Education, Vol. 50, No. 1
• Todd D. Reeves ,
• Douglas M. Warner ,
• Larry H. Ludlow , and
• Clare M. O’Connor
• James Hewlett, Monitoring Editor
• Learning High School Biology in a Social Context Creative Education, Vol. 08, No. 15
• A Symposium-Based Self-Directed Learning Approach to Teaching Medical Cell Biology to Medical Students 24 March 2016 | Medical Science Educator, Vol. 26, No. 2
• Student perceptions of the cell biology laboratory learning environment in four undergraduate science courses in Spain 15 December 2015 | Learning Environments Research, Vol. 19, No. 1
• Guided Inquiry and Consensus-Building Used to Construct Cellular Models Journal of Microbiology & Biology Education, Vol. 16, No. 1
• Brian A. Couch ,
• Tanya L. Brown ,
• Tyler J. Schelpat ,
• Mark J. Graham , and
• Jennifer K. Knight
• Michèle Shuster, Monitoring Editor
• Heather B. Miller ,
• D. Scott Witherow , and
• Susan Carson
• Elisa Stone, Monitoring Editor
• Using Class Poster Sessions to Teach Intermediary Metabolism The American Biology Teacher, Vol. 73, No. 3
• Using research to teach an “introduction to biological thinking” 28 January 2011 | Biochemistry and Molecular Biology Education, Vol. 39, No. 1
• Inter-institutional Development of a Poster-Based Cancer Biology Learning Tool 17 March 2010 | Journal of Cancer Education, Vol. 25, No. 3
• Peter Armbruster ,
• Maya Patel ,
• Erika Johnson , and
• Martha Weiss
• Debra Tomanek, Monitoring Editor
• Learning framework of “Integrating Techniques” for Solving Problems and Its Empirical Application in Doctoral Course in Mechanical Engineering Journal of JSEE, Vol. 57, No. 6
• Jonathan D. Knight ,
• Rebecca M. Fulop ,
• Leticia Márquez-Magaña , and
• Kimberly D. Tanner
• Martha Grossel, Monitoring Editor
• Increasing Scientific Literacy in Undergraduate Education 7 December 2009
• Students’ Perceptions of Terrascope, A Project-Based Freshman Learning Community 15 May 2007 | Journal of Science Education and Technology, Vol. 16, No. 4
• Deborah Allen , and
• Kimberly Tanner
• Laura Arwood
• Open Access: A PLoS for Education 11 May 2004 | PLoS Biology, Vol. 2, No. 5
• Susan M. DiBartolomeis , and
• James P. Moné
• Kimberly Tanner ,
• Liesl S. Chatman , and
• Deborah Allen

Submitted: 29 March 2002 Revised: 22 July 2002 Accepted: 29 July 2002

© 2002 by The American Society for Cell Biology

• collaborative learning
• upper-division cell biology
• team building
• project-based learning
• human diseases

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Collection  12 March 2021

2020 Top 50 Life and Biological Sciences Articles

We are pleased to share with you the 50 most downloaded Nature Communications articles* in the life and biological sciences published in 2020. (Please note we have a separate collection on the Top 50 SARS-CoV-2 papers .) Featuring authors from around the world, these papers highlight valuable research from an international community.

Browse all Top 50 subject area collections here .

* Data obtained from SN Insights (based on Digital Science's Dimensions) and has been normalised to account for articles published later in the year.

Vitamin D metabolites and the gut microbiome in older men

Here, the authors investigate associations of vitamin D metabolites with gut microbiome in a cross-sectional analysis of 567 elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study and find larger alpha-diversity correlates with high 1,25(OH)2D and high 24,25(OH)2D and higher ratios of activation and catabolism.

• Robert L. Thomas
• Lingjing Jiang
• Deborah M. Kado

The misuse of colour in science communication

The accurate representation of data is essential in science communication, however, colour maps that visually distort data through uneven colour gradients or are unreadable to those with colour vision deficiency remain prevalent. Here, the authors present a simple guide for the scientific use of colour and highlight ways for the scientific community to identify and prevent the misuse of colour in science.

• Fabio Crameri
• Grace E. Shephard
• Philip J. Heron

Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

The gut microbiota may contribute to depression, but the underlying mechanism is not well understood. Here the authors use a mouse model of stress induced depression to demonstrate that behavioural changes conferred by fecal transplant from stressed to naïve mice require the endocannabinoid system.

• Grégoire Chevalier
• Eleni Siopi
• Pierre-Marie Lledo

The default network of the human brain is associated with perceived social isolation

Here, using pattern-learning analyses of structural, functional, and diffusion brain scans in ~40,000 UK Biobank participants, the authors provide population-scale evidence that the default network is associated with perceived social isolation.

• R. Nathan Spreng
• Emile Dimas
• Danilo Bzdok

Non-invasive early detection of cancer four years before conventional diagnosis using a blood test

Patients whose disease is diagnosed in its early stages have better outcomes. In this study, the authors develop a non invasive blood test based on circulating tumor DNA methylation that can potentially detect cancer occurrence even in asymptomatic patients.

• Xingdong Chen
• Jeffrey Gole

Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure

Regulatory and coding regions of genes are shaped by evolution to control expression levels. Here, the authors use deep learning to identify rules controlling gene expression levels and suggest that all parts of the gene regulatory structure interact in this.

• Christoph S. Börlin
• Aleksej Zelezniak

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity

Antibody mediated immunity to SARS-CoV-2 will affect future transmission and disease severity. This systematic review on antibody response to coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and endemic coronaviruses provides insights into kinetics, correlates of protection, and association with disease severity.

• Angkana T. Huang
• Bernardo Garcia-Carreras
• Derek A. T. Cummings

Biomineral armor in leaf-cutter ants

Biomineral armour is known in a number of diverse creatures but has not previously been observed in insects. Here, the authors report on the discovery and characterization of high-magnesium calcite armour which overlays the exoskeletons of leaf-cutter ants.

• Chang-Yu Sun
• Cameron R. Currie

Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation

Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.

• Jasper Iske
• Midas Seyda
• Stefan G. Tullius

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial

Preclinical evidence suggests that a fasting mimicking diet (FMD) can make cancer cells more vulnerable to chemotherapy, while protecting normal cells. In this randomized phase II clinical trial of 131 patients with HER2 negative early stage breast cancer, the authors demonstrate that FMD is safe and enhances the effects of neoadjuvant chemotherapy on radiological and pathological tumor response.

• Stefanie de Groot
• Rieneke T. Lugtenberg
• Dutch Breast Cancer Research Group (BOOG)

Aerobic microbial life persists in oxic marine sediment as old as 101.5 million years

The discovery of aerobic microbial communities in nutrient-poor sediments below the seafloor begs the question of the mechanisms for their persistence. Here the authors investigate subseafloor sediment in the South Pacific Gyre abyssal plain, showing that aerobic microbial life can be revived and retain metabolic potential even from 101.5 Ma-old sediment.

• Yuki Morono
• Fumio Inagaki

The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice

Auxin-inducible degron systems can be leaky and require high doses of auxin. Here the authors establish AID2 which uses an OsTIR1 mutant and the ligand 5-Ph-IAA to overcome these problems and establish AID-mediated target depletion in mice.

• Aisha Yesbolatova
• Yuichiro Saito
• Masato T. Kanemaki

Origin and cross-species transmission of bat coronaviruses in China

Bats are a likely reservoir of zoonotic coronaviruses (CoVs). Here, analyzing bat CoV sequences in China, the authors find that alpha-CoVs have switched hosts more frequently than betaCoVs, identify a bat family and genus that are highly involved in host-switching, and define hotspots of CoV evolutionary diversity.

• Alice Latinne
• Peter Daszak

Multivariate genomic scan implicates novel loci and haem metabolism in human ageing

Ageing phenotypes are of great interest but are difficult to study genetically, partly due to the sample sizes required. Here, the authors present a multivariate framework to combine GWAS summary statistics and increase statistical power, identifying additional loci enriched for aging.

• Paul R. H. J. Timmers
• James F. Wilson
• Joris Deelen

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

Mircobial symbionts of mosquitoes can affect transmission of human pathogens. Here, Herren et al . identify a microsporidian symbiont in Anopheles gambiae that impairs transmission without affecting mosquito fecundity or survival.

• Jeremy K. Herren
• Lilian Mbaisi
• Steven P. Sinkins

Gene editing and elimination of latent herpes simplex virus in vivo

Herpes simplex virus establishes lifelong latency in ganglionic neurons, which are the source for recurrent infection. Here Aubert et al. report a promising antiviral therapy based on gene editing with adeno-associated virus-delivered meganucleases, which leads to a significant reduction in ganglionic HSV loads and HSV reactivation.

• Martine Aubert
• Daniel E. Strongin
• Keith R. Jerome

A predictive index for health status using species-level gut microbiome profiling

A biologically-interpretable and robust metric that provides insight into one’s health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, the authors introduce a species-level index that predicts the likelihood of having a disease.

• Vinod K. Gupta
• Jaeyun Sung

Bacterial nanotubes as a manifestation of cell death

Bacterial nanotubes and other similar membranous structures have been reported to function as conduits between cells to exchange DNA, proteins, and nutrients. Here the authors provide evidence that bacterial nanotubes are formed only by dead or dying cells, thus questioning their previously proposed functions.

• Jiří Pospíšil
• Dragana Vítovská
• Libor Krásný

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Intermittent fasting (IF) has been shown beneficial in reducing metabolic diseases. Here, using a multi-omics approach in a T2D mouse model, the authors report that IF alters the composition of the gut microbiota and improves metabolic phenotypes that correlate with cognitive behavior.

• Zhigang Liu
• Xiaoshuang Dai

Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells

Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.

• Tapash Jay Sarkar
• Marco Quarta
• Vittorio Sebastiano

Mitochondrial TCA cycle metabolites control physiology and disease

Mitochondrial metabolites contribute to more than biosynthesis, and it is clear that they influence multiple cellular functions in a variety of ways. Here, Martínez-Reyes and Chandel review key metabolites and describe their effects on processes involved in physiology and disease including chromatin dynamics, immunity, and hypoxia.

• Inmaculada Martínez-Reyes
• Navdeep S. Chandel

A deep learning model to predict RNA-Seq expression of tumours from whole slide images

RNA-sequencing of tumour tissue can provide important diagnostic and prognostic information but this is costly and not routinely performed in all clinical settings. Here, the authors show that whole slide histology slides—part of routine care—can be used to predict RNA-sequencing data and thus reduce the need for additional analyses.

• Benoît Schmauch
• Alberto Romagnoni
• Gilles Wainrib

Circadian regulation of mitochondrial uncoupling and lifespan

Disruption of different components of molecular circadian clocks has varying effects on health and lifespan of model organisms. Here the authors show that loss of period extends life in drosophila melanogaster.

• Matt Ulgherait
• Mimi Shirasu-Hiza

Circadian control of brain glymphatic and lymphatic fluid flow

Glymphatic function is increased during the rest phase while more cerebrospinal fluid (CSF) drains directly to the lymphatic system during the active phase. The water channel aquaporin-4 supports these endogenous, circadian rhythms in CSF distribution.

• Lauren M. Hablitz
• Virginia Plá
• Maiken Nedergaard

Brain-inspired replay for continual learning with artificial neural networks

One challenge that faces artificial intelligence is the inability of deep neural networks to continuously learn new information without catastrophically forgetting what has been learnt before. To solve this problem, here the authors propose a replay-based algorithm for deep learning without the need to store data.

• Gido M. van de Ven
• Hava T. Siegelmann
• Andreas S. Tolias

Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy

Glioblastoma is thought to arise from neural stem cells. Here, to investigate this, the authors use single-cell RNA-sequencing to compare glioblastoma to the fetal human brain, and find a similarity between glial progenitor cells and a subpopulation of glioblastoma cells.

• Charles P. Couturier
• Shamini Ayyadhury
• Kevin Petrecca

Deep learning for genomics using Janggu

Deep learning is becoming a popular approach for understanding biological processes but can be hard to adapt to new questions. Here, the authors develop Janggu, a python library that aims to ease data acquisition and model evaluation and facilitate deep learning applications in genomics.

• Wolfgang Kopp
• Altuna Akalin

Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues

Tissue clearing has revolutionised histology, but limited penetration of antibodies and stains into thick tissue segments is still a bottleneck. Here, the authors characterise optically cleared tissue as an electrolyte gel and apply this knowledge to stain the entirety of thick tissue samples.

• Etsuo A. Susaki
• Chika Shimizu
• Hiroki R. Ueda

Sestrins are evolutionarily conserved mediators of exercise benefits

Exercise improves metabolic health and physical condition, particularly important for health in aged individuals. Here, the authors identify that Sestrins, proteins induced by exercise, are key mediators of the metabolic adaptation to exercise and increase endurance through the AKT and PGC1a axes.

• Myungjin Kim
• Alyson Sujkowski
• Jun Hee Lee

Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers

Fasting diets are emerging as an approach to delay tumor progression and improve cancer therapies. Here, the authors show that the combination of fasting-mimicking diet with vitamin C decreases tumor development and increases chemotherapy efficacy in KRAS-mutant cancer.

• Maira Di Tano
• Franca Raucci
• Valter D. Longo

Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma

Understanding the mechanisms that lead to lung adenocarcinoma metastasis is important for identifying new therapeutics. Here, the authors document the changes in the transcriptome of human lung adenocarcinoma using single-cell sequencing and link cancer cell signatures to immune cell dynamics.

• Nayoung Kim
• Hong Kwan Kim
• Hae-Ock Lee

A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

• Gurnit Atwal
• PCAWG Consortium

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression

Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

• Anna S. E. Cuomo
• Daniel D. Seaton
• Oliver Stegle

Trajectory-based differential expression analysis for single-cell sequencing data

Downstream of trajectory inference for cell lineages based on scRNA-seq data, differential expression analysis yields insight into biological processes. Here, Van den Berge et al. develop tradeSeq, a framework for the inference of within and between-lineage differential expression, based on negative binomial generalized additive models.

• Koen Van den Berge
• Hector Roux de Bézieux
• Lieven Clement

Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome

Here, Pasolli et al. perform a large-scale genome-wide comparative analysis of publicly available and newly sequenced food and human metagenomes to investigate the prevalence and diversity of lactic acid bacteria (LAB), indicating food as a major source of LAB species in the human gut.

• Edoardo Pasolli
• Francesca De Filippis
• Danilo Ercolini

Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia

Ancient DNA analysis of early European farmers has found a high level of genetic affinity with present-day Sardinians. Here, the authors generate genome-wide capture data for 70 individuals from Sardinia spanning the Middle Neolithic to Medieval period to reveal relationships with mainland European populations shifting over time.

• Joseph H. Marcus
• Cosimo Posth
• John Novembre

Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome

Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum.

• Matthias Arnold
• Kwangsik Nho
• Gabi Kastenmüller

Integrative pathway enrichment analysis of multivariate omics data

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

• Marta Paczkowska
• Jonathan Barenboim

Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice

Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.

• Stephanie J. Alexopoulos
• Sing-Young Chen
• Kyle L. Hoehn

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects.

• Yann W. Yap
• Patricia M. Rusu
• Adam J. Rose

Multiplexed CRISPR technologies for gene editing and transcriptional regulation

Multiplexed CRISPR technologies have recently emerged as powerful approaches for genetic editing and transcriptional regulation. Here the authors review this emerging technology and discuss challenges and considerations for future studies.

• Nicholas S. McCarty
• Alicia E. Graham
• Rodrigo Ledesma-Amaro

Determining sequencing depth in a single-cell RNA-seq experiment

For single-cell RNA-seq experiments the sequencing budget is limited, and how it should be optimally allocated to maximize information is not clear. Here the authors develop a mathematical framework to show that, for estimating many gene properties, the optimal allocation is to sequence at the depth of one read per cell per gene.

• Martin Jinye Zhang
• Vasilis Ntranos

Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels

Ceramides are a type of sphingolipid (SL) that have been shown to play a role in several metabolic disorders. Here, the authors investigate the effect of SL-production by gut Bacteroides on host SL homeostasis and show that microbiome-derived SLs enter host circulation and alter ceramide production.

• Elizabeth L. Johnson
• Stacey L. Heaver
• Ruth E. Ley

Ancient genomes reveal social and genetic structure of Late Neolithic Switzerland

European populations underwent strong genetic changes during the Neolithic. Here, Furtwängler et al. provide ancient nuclear and mitochondrial genomic data from the region of Switzerland during the end of the Neolithic and the Early Bronze Age that reveal a complex genetic turnover during the arrival of steppe ancestry.

• Anja Furtwängler
• A. B. Rohrlach
• Johannes Krause

Brain insulin sensitivity is linked to adiposity and body fat distribution

Brain insulin action regulates eating behavior and whole-body energy fluxes, however the impact of brain insulin resistance on long-term weight and body fat composition is unknown. Here, the authors show that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution.

• Stephanie Kullmann
• Vera Valenta
• Martin Heni

Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair

Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.

• Filipa C. Simões
• Thomas J. Cahill
• Paul R. Riley

Sexual-dimorphism in human immune system aging

Whether the immune system aging differs between men and women is barely known. Here the authors characterize gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age, uncovering shared as well as sex-unique alterations, and create a web resource to interactively explore the data.

• Eladio J. Márquez
• Cheng-han Chung

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.

• Tatsuya Tsukui
• Kai-Hui Sun
• Dean Sheppard

Pathway and network analysis of more than 2500 whole cancer genomes

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

• Matthew A. Reyna

Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4 + T cells to cytokines

Cytokines critically control the differentiation and functions of activated naïve and memory T cells. Here the authors show, using multi-omics and single-cell analyses, that naïve and memory T cells exhibit distinct cytokine responses, in which an ‘effectorness gradient’ is depicted by a transcriptional continuum, which shapes the downstream genetic programs.

• Eddie Cano-Gamez
• Blagoje Soskic
• Gosia Trynka

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Top 100 biology research topics for high school and college.

Writing a biology essay may not sound like a very difficult thing to do. In fact, most students really like this subject. The problem is not that you can’t write a good paper on a topic in biology. The problem is with finding excellent biology research topics. Now, you may be wondering why you would want to invest so much time into finding great biology research paper topics. After all, what you write in the essay matters more than the topic, right? Wrong! We are here to tell you that professors really appreciate interesting and unique topics.

And it makes a lot of sense, if you think about it. If you simply pick one of the most popular biology research topics, you will never be able to pique the interest of your teacher. He has read dozens, if not hundreds, or papers on that exact same topic. What you want to do is come up with interesting biology research topics. You want to find topics that none of your classmates are thinking of writing an academic paper about. You will shortly see why this is important. And we will also give you 100 biology topics for research projects that you can use for free – right now!

Biology Research Paper Topics Really Are Important!

It doesn’t matter what area of biology you need to write about. This information applies to everything from zoology and botany to anatomy. The reality is that your professor will really appreciate good topics. And you can rest assured that he or she knows how to spot them. The moment the professor starts to read your paper, he or she will immediately realize that you really did your best to find an excellent topic. And if you write a good introduction paragraph (which contains a captivating thesis statement as well), you are in the best position to earn bonus points.

You may not be aware of it, but teachers are willing to treat great papers with more leniency. This means that you will not get penalized for minor mistakes if you come up with a great topic. In other words, you will get a better grade on your papers if you manage to come up with good research topics for biology. This is a fact and it is based on thousands of pieces of feedback from our readers.

How Do You Choose Good Biology Research Topics?

Choosing research topics for biology can be a daunting task. Frankly, the research paper topics biology students are looking for are not easy to come by. The first thing you want to avoid is going to the first website that pops up in Google and getting your ideas from there. Most of your peers will do the same. Also, avoid topics that are extremely simple. You will simply not have enough ideas to write about. Of course, you should avoid overly complex topics because finding information about them may be extremely difficult.

The best way to find a good topic, in our opinion, is to get in touch with an academic writing company. You will get access to a professional writer who knows exactly what professors are looking for. A writer will quickly give you an amazing research topic in biology.

Eloquent Examples of Popular Biology Research Topics

To make things as simple as possible for you, we’ve put together a list of biology research project ideas. You will find 100 topics on various subjects below. Of course, you can use any of our topics for free. However, keep in mind that even though we are doing our best to maintain this list fresh, other students will find it as well. If you need new topics for your next biology essay, we recommend you to get in touch with us. We monitor our email address, so we can help you right away. Also, you can buy a research paper from our service.

Biology Research Topics for High School

Are you looking for biology research topics for high school? These are relatively simple when compared to college-level topics. Here are a couple of topic ideas that high school students will surely appreciate:

• Identifying Three Dead Branches of Evolution.
• What Is Sleep?
• How Does Physical Exercise Affect the Metabolism?
• A Behavioral Study of Birds.
• How Does Music Affect Your Brain?
• Climate Change and Biodiversity.
• Are Bees Really Becoming Extinct?
• Rainforest Extinction Is Dangerous.
• The Benefits of Organic Farming.
• Can the Brain Repair Itself?
• The Effect of Bacteria on Depression.
• How Do Sea Animals Camouflage?

Research Topics in Biology for Undergraduates

Research topics in biology for undergraduates are more complex than high school or college topics. Our researchers did their best to find topics that are relatively complex. However, each one of the following topics has plenty of information about it online:

• What Is the Mechanism of Metastasis in Cancer Patients?
• How Do Tumor Suppressor Genes Appear?
• How Can We Destroy Cancer Cells Without Damaging Other Cells?
• The Benefits of Gene Therapy.
• Analyzing the Huntington’s Disease (the HTT Gene).
• How Does the down Syndrome (Trisomy of 21st Chromosome) Appear?
• Analyzing the Brain Activity During an Epileptic Seizure.
• How Are Our Memories Formed and Preserved?
• The Effect of Probiotics on Infections.
• Analyzing Primate Language.
• Analyzing Primate Cognitive Functions.
• The Link Between Darwin’s Theory and Biology.

Biology Research Topics for College Students

Biology research topics for college students are of moderate difficulty. They are easier than undergrad topics and more complex than high school topics. While compiling this list, we made sure you have more than enough information online to write the paper quickly:

• Using DNA Technology in the Field of Medical Genetics.
• The Effect of Drinking on Embryonic Development.
• How Are Genes Mapped and Cloned?
• Explain What Genetic Polymorphism Is.
• What Is a Hereditary Disease?
• The Effect of Drugs on Embryonic Development.
• Describing Oligogenic Diseases (like Hirschsprung Disease)
• What Is the Mendelian Inheritance?
• How Transcriptomics and Proteomics Changed Modern Medicine.
• The Risk Factors of Infertility Explained.
• How Does Aging Effect Infertility?
• What Do Ash Elements Do in a Plant?
• Explaining the Pigments in a Plant Cell.
• How Is Photosynthesis Done?
• The Role of Fats in Plant Cells.
• The Effect of Smoking on Embryonic Development.

Cell Biology Research Topics

Some of the best biology topics are cell biology research topics. The scientific community is constantly making progress in this area, so there is always something new to write about. Here are some of the best examples:

• What Is Regenerative Medicine?
• A Closer Look at Tissue Engineering.
• Discuss the Future of Regenerative Medicine.
• Analyzing Therapeutic Cloning.
• The Pros and Cons of Creating Artificial Organs.
• How Do Cell Age?
• Can We Reverse Cell Aging?
• Advances in Cell Therapy.
• What Is Cell Adhesion?
• Explaining Cell Division.
• What Is Cellular Metabolism?
• Describe Active and Passive Transport in Cells.
• What Are Cell Plastids?

Evolutionary Biology Research Paper Topics

If you want something more complex, you can try your hand at writing on evolutionary biology research paper topics. As with all our topics, you will be able to find a lot of ideas and information online. Here are our picks:

• Where Did Plants Come From? (The Evolutionary Theory)
• Explaining the Host-parasite Coevolution.
• How Did Parasites Evolve over Time?
• What Is Natural Selection and How Does It Work?
• Explain Sexual Selection.
• Explain Sexual Conflict.
• How Did Our Immune Systems Evolve?
• How Do New Species Appear in the Wild?
• The Evolution of Cell Respiration.
• What Is the Hippo Pathway? (Developmental Biology)

Various Topics

Antibiotics resistance, agriculture and cloning are hot subjects nowadays. Your professor will surely be interested to learn more about biology research topics. Here is a mix of topic ideas from our established community of academic writers:

• The Problem of Using Antibiotics on Large Scale.
• Examining the Effects of Salt on Plants.
• What Is DNA Technology?
• The Effects of GMOs on the Human Body.
• How Is the Quality of Antibiotics Controlled?
• How Are GMO Food Crops Created?
• The Effect of Veterinary Antibiotics on Humans.
• The Allergic Reactions to Specific Antibiotics.
• A Look at How Penicillin Works in the Human Body.
• How Are Antibiotics Obtained?
• What Are Natural Biochemicals with Pest-repellent Properties?
• The 3 Most Toxic Effects of Antibiotics
• How the Human Body Develops Resistance to Antibiotics.
• The Impact of Biology on the Us Agriculture.
• What Is the Green Revolution?
• Analyzing the Minerals in the Plant Cell.
• Analyzing Muscle Development and Regeneration
• The Uses of Cancer Stem Cells.

Marine Biology Research Topics

There is a lot of talk about global warming, about microplastics in our oceans, and about endangered marine species. This means that marine biology research topics are a very hot topic today. Here are some of our best ideas:

• Can GMO Organisms Break down Oil after Maritime Accidents?
• Pollution-absorbing Bio-films.
• Microbes That Can Absorb Toxic Compounds in the Water.
• Can We Really Use Bioluminescence?
• How Is Bio-diesel Created?
• Analyzing the Coral Reef Biology.
• Why Is the Lobster Population Dwindling?
• The Effect of Mass Fishing on the World’s Oceans.
• Global Warming and Its Effect on Marine Microorganisms.

Molecular Biology Research Topics

Writing about molecular biology research topics is not easy. However, it’s a foolproof way to get a top grade. Your professor will really appreciate your willingness to write an essay about a complex topic. Just make sure you know what you are talking about. Below you can find some of the best topics:

• How Is Insulin Produced?
• How Is the Growth Hormone Produced?
• Analyzing the Repropagation of Translation.
• What Is DNA-telomerase?
• The Process of Sequencing Nucleotides in DNA.
• What Is Telomerase?
• The Link Between Telomerase and Cancer.
• The Link Between Telomerase and Aging.
• How Does DNA Forensics Work?
• Describe the Process of Protein Metabolism.

There is no such thing as easy biology research topics. When the topic is too simple, you end up getting penalized. You can’t write 500 words about it without straying away from the subject. Also, no matter how interesting the topic may be, you should make sure that the essay is written perfectly. This means that not even interesting biology research topics can save you from a bad grade if you fail to follow all applicable academic writing standards.

Find it hard to cope with your college paper? Great news! Use promo “ mypaper20 ” and enjoy 20% discount on a biology writing assignment from our profs!

Biology Science Fair Project Ideas

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• Cell Biology
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How to Find Science Project Ideas

Plant project ideas.

• Human Body Project Ideas

Animal Project Ideas

Researching your science project ideas.

• B.A., Biology, Emory University
• A.S., Nursing, Chattahoochee Technical College

Science fair projects give you the opportunity to experience science and biology through hands-on activities . In order to ensure that you have a great biology project, it is important that you first understand biology and the scientific method . Simply put, biology is the study of life. Life is all around us which means that there are enormous possibilities when considering a biology science project. We use the scientific method as a means of studying science and biology. Scientific inquiry starts with an observation followed by the formulation of a question about what has been observed. Then comes designing a scientific experiment to answer the question posed.

So where do you get ideas for biology science fair projects? The answer is from almost anywhere. The key is to start with a question that you would like to find an answer to and use the scientific method  to help you answer it. When choosing a science fair project topic , make sure that you select a topic that you are interested in. Then narrow this topic down to a specific question.

Below you will find science fair project ideas primarily related to biology. Remember that these samples are meant to give direction and ideas. It is important that you do the work yourself and not just copy the material. Also, be sure that you know all of the rules and regulations for your particular science fair before you begin your project.

Plants are important to life as we know it. They provide everything from food, clothing, and shelter to medicine and fuel. Plant projects are popular because plants are abundant, inexpensive, and relatively easy to study during experimentation. These experiments allow you to learn about plant processes and environmental factors that impact plant life.

• Plant-based science projects : Find more than 20 ideas for science fair projects involving plants.
• Soil chemistry : Learn about soil chemistry with these example projects about plant science and the chemical composition of soil.
• Popcorn studies : Enjoy these fun, easy, and interesting experiments with popcorn.

If you have ever wondered how the body works or about all the biological processes that keep the body functioning, then you should consider a science project on the human body. These projects allow you to gain a better knowledge of how the body functions and also provide insight into human behavior.

• Human body projects : If your interest is in biological processes and human behavior, this resource has several ideas for projects on the human body, including the study of the effects of music, temperature, and video games on mood.
• Kids' neuroscience experiments : This is a nice collection of experiments relating to neuroscience. It includes projects dealing with reflexes, the nervous system , biological rhythms, and more.
• Human hair projects : Find several ideas for doing projects about hair. Topics include hair growth rates and hair loss management.

Animal science projects allow us to understand various aspects of animal life. They provide information about animal anatomy, behavior, and even provide insight into human biological processes. Before deciding to do an animal project, be sure that you get permission and avoid animal cruelty. Some science fairs do not allow animal experiments, while others have strict regulations for animal usage.

• Animal projects : Find great ideas for projects involving insects, birds, amphibians, fish, and mammals. Discover how light, pollution, and magnetic fields affect animals.

After you have come up with an idea and topic for your science project, you must research your topic. Research involves finding out everything you can about the scientific principles involved with your project idea. There are several resources available for researching your science fair project. Some of these include your local library, science books and magazines, internet science news sources, and teachers or educators. The most helpful thing that you can do when researching for your project is to take excellent notes.

• Record references for the books and other materials you have used in your research.
• Take notes on simple experiments on which to base your experiment. 
• Keep notes on diagrams used in similar experiments. 
• Record observations from other experiments.
• Keep notes on samples of logs and other means for collecting data. 
• Make lists of materials that you might want to order and their suppliers.

It is important that keep track of all the resources used in your research as these source materials will be required for listing in the bibliography for your science fair project report.

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• How to Write a Bibliography For a Science Fair Project
• How to Do a Science Fair Project
• 5 Types of Science Fair Projects
• What Judges Look for in a Science Fair Project
• How to Select a Science Fair Project Topic
• How to Organize Your Science Fair Poster
• How to Write a Science Fair Project Report
• High School Science Fair Projects
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• Animal Science Fair Project Ideas
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17 Creative Plant Cell Project Ideas To Try This Year

These ideas won’t leaf you disappointed!

Making science come alive in the classroom is important because it helps keep students engaged. By fifth grade, most students begin to learn some biology basics, including what a plant cell is and how it’s structured. While many plant cell project ideas and lessons are geared toward upper elementary school students, the simpler concepts can be taught to younger students using supplies like play dough.

Whether you have your students create 3D plant cell projects in school or as part of a take-home assignment, they can really help kids better understand cells and their organelles. A plant cell project can be complicated (stitching a cell), but many are fairly easy and require little more than the supplies you likely already have on hand.

3D Plant Cell Projects

1. jelly plant cell model.

First, you’ll need to make Jell-O in a lightly greased container. Then, you’ll add candies to represent each organelle. Finally, use toothpicks and stickers to label everything. Bonus: Once you’re finished, you get to eat the leftover candy!

Learn more: Jell-O Plant Cell Model at Science Sparks

2. Clay Model

Grab some Air-Dry Modeling Clay and then get building! Print out the various names of the parts of the cell, including the cell wall and membrane, and then create little flags out of them with toothpicks.

3. Altoids Model

These Altoids tins make for the perfect and oh-so adorably pocket-sized home for a mini 3D plant cell model. You can use card stock to make the various parts of the model and then use two layers of mounting tape or craft foam to make it pop.

Learn more: 3D Mint Tin Cell Model at Teacher Thrive

4. Cardboard Plant Cell Model

This one is somewhat time-consuming, but it requires little more than some recycled cardboard and construction paper or card stock. If a younger child is doing this project, you’ll want an adult to handle the X-Acto knife.

5. Plant Cell Model From Seeds

This 3D plant cell project will take a while, but the results will be well worth it. We especially love the idea of using seeds to create the various parts of the plant cell!

6. LEGO Plant Cell

Kids love LEGO so why not incorporate them into your science unit on plant and animal cells?

7. Plant Cell Cake

This idea is so creative and all you need is a cake pan, frosting, and some candy. Add some toothpicks with labels and your delicious cake just became educational!

8. Stitched Model

You’ll definitely want to have sewing experience before tackling this plant cell project. Since it is time-consuming and requires skill, we think it would be perfect for a handy teacher to create to use as a teaching tool.

Learn more: Stitched Plant Cell at Becky Button

9. Peanut Butter Cell

Another edible option! This one is so simple that it will be easy for young kids to recreate. Since some kids have peanut allergies, you can replace the peanut butter with a more allergy-friendly spread. And you’ll have a tasty treat once the learning is done!

Learn more: Edible Cell Model for Elementary School at Adventures in Mommydom

10. Play-Doh Model

Kids love playing with Play-Doh, so they will really enjoy creating an animal or plant cell in different colors. We especially love that supplies are minimal. Creating each individual part of the plant cell will help kids remember their names and purposes.

Learn more: Introducing Animal and Plant Cells to Kids at Spongy Kids

11. Whole-Class Plant Model

This idea takes a 3D plant cell project to the next level! Students are divided into groups by organelles and then they need to create a blueprint for and build their plant cell component to scale. The giant plant cell is created from clear painter’s drop cloths and then inflated using fans. This activity will engage all your students while also being fun and educational.

Learn more: Biology Students and the Giant Plant Cell at Teachers Network

Other Plant Cell Projects

12. plant cell drawing tutorial.

Kids love to follow drawing tutorials, and this one will be no exception. The muscle memory involved in actually drawing each part should help them with remembering the various components of the plant cell.

13. Rock ‘n Learn Video

This cute video uses relatable characters to teach about the different parts of a plant cell while also highlighting the differences between plant and animal cells.

14. Two-Minute Lesson

This is another video lesson, but this one is geared toward slightly older kids. It’s a great video for kids to bookmark so they can refresh their memories later.

15. Shrinky Dinks Model

Shrinky Dinks have been around for decades, so many teachers and parents probably remember crafting with them at some point in their childhood. They are essentially thin sheets of plastic that you cut and color and then bake in an oven. Once baked, you have a tiny version of what you created.

Learn more: Shrinky Dinks Cell Models at Teacher Thrive

16. Cut-and-Paste Worksheet

These worksheets are a great way to introduce the concept of a plant cell and the various organelles. Grab scissors and glue sticks and get to work learning about plant cells and their organelles!

Learn more: Free Build-Your-Own Animal and Plant Cell Worksheet at You’ve Got This Math

17. A Complete Lesson Plan

This is a complete lesson plan that has students travel to different stations while learning all about animal and plant cells. Students will learn different things when making their way through the four E’s in this plan—engagement, exploration, explanation, and elaboration.

Learn more: Plant and Animal Cell Lesson at Kesler Science

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