medical research centre uk

NIHR Manchester Biomedical Research Centre

The National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC) is the largest BRC outside the South East of England and the beating heart of translational research across Greater Manchester, Lancashire and South Cumbria, transforming scientific breakthroughs into diagnostic tests and life-saving treatments for patients.

Awarded more than £60 million (2022-27) – the largest single research award given by the NIHR to the city region – Manchester BRC brings together world-leading researchers based at The University of Manchester and six of the country’s foremost NHS Trusts, with a vision to drive health improvements and lasting change for all through creative, inclusive and proactive research that identifies and bridges gaps between new discoveries and individualised care.

Manchester BRC is driving forward pioneering research in the areas of cancer (prevention and early detection, advanced radiotherapy, precision medicine, living with and beyond cancer), inflammation (rheumatic and musculoskeletal disease, respiratory medicine, dermatology, integrative cardiovascular medicine), high-burden under-researched conditions (hearing health, mental health, rare conditions) and advanced diagnostics and therapeutics (next generation phenotyping and diagnostics, next generation therapeutics).

Recent News & Events

The power of your data to advance arthritis research – louise cook, prof will dixon and dr meghna jani speak to arthritis digest magazine.

For Arthritis Digest magazine, Louise Cook, Professor Will Dixon and Dr Meghna Jani explain how analysis of health data could help improve the lives and care of people living with arthritis.

New method could lower radiotherapy doses for some cancer patients

A special type of MRI scan where patients inhale 100% oxygen could result in lower radiotherapy doses for some cancer patients.

Introducing the NIHR Manchester BRC

You can help shape our research

There are plently of opportunities for people to help shape our research plans. Research is vital to help us understand more about a particular disease or condition and how to treat them.

Our research

Explore our 13 research themes.

MRC Impact Showcase

How the people and projects we invest in at the Medical Research Council (MRC) are making an impact on our lives and the world we live in.

Our mission at the Medical Research Council (MRC), part of UK Research and Innovation, is to improve human health through world-class medical research. To achieve this, we invest public money into some of the best medical rese arch in the world across every area of health. Our work has led to some of medicine’s biggest breakthroughs – from deciphering DNA’s structure to inventing the MRI scanner and developing the first COVID-19 vaccine. Our scientists have transformed modern medicine, and in turn have been recognised by 32 Nobel Prizes.

The impacts of our work are broad and diverse – benefiting the economy, society, culture, public policy and services, health, the environment, and quality of life for people in the UK and around the world. They are made possible not just through funding science, but also through targeted investment supporting entrepreneurial activity and supporting enterprise. MRC has built up emerging areas and funded world-class ideas, working with stakeholders across all sectors and partners across the world, guided by our vision to accelerate improvements in human health and economic prosperity.

The case studies below showcase just some of the non-academic impacts arising from MRC funding, with examples from higher education institutes (HEIs) and MRC-supported institutes and major investments.

Credit: Dr Daniyal Jafree and Professor David Long, Kidney Development and Disease Group, UCL Great Ormond Street Institute of Child Health

MRC supporting jobs and boosting the UK economy

First gene therapies for haemophilia, and creation of spin-out Freeline Therapeutics

• UCL developed single-dose gene therapy that restores blood-clotting and can be delivered at 1% of the cost of conventional treatment – changing the lives of thousands with haemophilia
• The inherited disorder causes internal bleeding and significantly affects 800,000 affected men and boys worldwide
• Therapies have treated over 300 patients in clinical trials to date, and a spin-out company, Freeline Therapeutics, was launched in 2015 to develop the approach
• MRC funding has supported the underpinning haemophilia research for over 60 years

New cancer therapies insight leads to spin-out companies worth £54m and 326 new jobs

• Research into how cancer cells interact with the immune system has led to new avenues for developing treatments
• Researchers at the Francis Crick Institute – a partnership between MRC, Cancer Research UK and Wellcome – have identified several unique cellular processes involved in driving cancer growth, providing opportunities to develop targeted therapies aimed at disrupting them
• The research has led to several spin-out companies, collectively valued at £54.4m and employing 326 people, with several therapeutic candidates in phase I/II trials for melanoma, solid cancers and leukaemia

Creating the world’s largest retinal gene therapy company

• Gene-therapy research into inherited diseases that cause blindness led to new treatments and the formation of a successful spin-out company
• MRC-funded research at Imperial College London and the University of Oxford pioneered the first clinical trials of gene therapy for the diseases choroideremia and X-linked retinal pigmentosa, which demonstrated significant improvement in vision for some of the patients treated
• Spin-out company Nightstar was created with the novel treatment as its lead programme. Licensing of subsequent research extended the approach to other kinds of retinal pigmentosa, and created the world’s largest retinal gene therapy company

MRC tackling the impact of COVID-19

Global adoption of effective COVID-19 treatments saves lives

• RECOVERY trial (Randomised Evaluation of COVID-19 Therapy) – world’s largest clinical trial into treatments for COVID-19, more than 48,000 participants across 185 sites
• Results found dexamethasone, a cheap, readily available steroid, reduces death rates among seriously unwell patients
• Findings immediately transformed global clinical guidelines and practice
• MRC funding directly supported RECOVERY trial through the COVID-19 Rapid Response Initiative in 2020 with the National Institute of Health Research
• The initiative saved an estimated 650,000 lives by the end of 2020
•   Find out more about the RECOVERY trial

Oxford-AstraZeneca Covid-19 vaccine contributed to 6.3m lives saved

• Oxford-AstraZeneca COVID-19 vaccine contributed to saving 6.3 million lives around the world in the first year of rollout
• More than 11,000 trial participants showed 70% reduced risk of COVID-19 and 100% reduction in risk of hospitalisation or death
• MRC funding supported vaccine’s development – success underpinned by decades of MRC funded research that supported the development of ChAdOx1 platform – an adenoviral vector for vaccines to induce and boost cellular immunity
•   Find out more about our role in developing the vaccine

Coronavirus samples inform national COVID-treatment guidelines

• Sotrovimab was one of the first anti-viral therapies licensed for the treatment of COVID-19 and an essential defence for people who have a poorer response to vaccination. However, by 2022 there was concern sotrovimab may not respond to newer variants circulating
• Led by researchers at the MRC-funded Francis Crick Institute, the Legacy Study utilised a unique bank of more than 400,000 coronavirus samples that had been collected since 2020 to test a variety of therapies
• They were able to show sotrovimab offered protection against newer strains. As a result, NICE issued guidelines for its continued use

UK Biobank provides evidence of COVID-19 brain changes

• Brain scans from UK Biobank – a database established by MRC with genetic and health information from 500,000 UK participants – revealed how even mild COVID-19 infection can cause physical changes to the brain
• The UK Biobank COVID-19 Repeat Imaging study enabled researchers to access brain scans of individuals around three years apart, making it the only study in the world to demonstrate ‘before and after’ changes in the brain associated with SARS-CoV02 infection
• The results showed participants who contracted COVID-19 had a greater reduction in brain size compared to uninfected participants. UK Biobank will be a vital resource in understanding whether these changes are reversible over time

UK Biobank participant undergoing a brain scan as part of the UK Biobank COVID-19 Repeat Imaging study. Credit: UK Biobank

MRC improving UK health and wellbeing

Lifesaving treatments for neuromuscular diseases in children

• More than two million children worldwide are affected by neuromuscular diseases
• Work funded by MRC and medical research charities, in collaboration with biotechnology companies, led to approval of the first effective treatments for the genetic diseases Duchene Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA)
• Researchers from UCL, Royal Holloway and Bedford New College developed Spinraza – the only approved drug for the treatment of SMA in the UK and most of the world – available via the NHS since June 2019, with 300 patients already gaining access
• Two medicines developed for DMD – Exondys 51 and Vyondys 53 – which improve quality of life and life expectancy for at least 20% of patients, approved in the US and benefitting over 1,500 people so far
• These medicines have also generated sales of more than $5.5 billion

Cell discovery offers potential new asthma treatment

• The discovery of a type of immune cell could provide a valuable new tool for treating asthma
• Researchers at the MRC-funded Laboratory of Molecular Biology discovered cells that secrete an inflammatory molecule, interleukin-13 (IL-13), which can trigger a reaction in asthma patients. The release of IL-13 is activated by interleukin-25 (IL-25)
• Scientists developed a therapy to block the action of IL-25, preventing it from activating IL-13 and triggering an asthma reaction. A clinical trial is underway to establish its use in treating asthma. The therapy also has potential in the treatment of colorectal cancer

Microscope images of a mouse intestine showing smaller cancers and a more active immune response when ILC2 immune cells are blocked or removed. Credit: MRC Laboratory of Molecular Biology

Repairing damaged cartilage in knee joints

• Left untreated, defects in cartilage can progress to osteoarthritis. A team of researchers at the University of Keele has developed a cell therapy that helps repair cartilage in knee joints
• An MRC-funded trial provided the evidence and cost-benefit data that led to the therapy, known as autologous chondrocyte implantation, which received NICE approval in 2017. The team also developed a tool to help identify patients who would most benefit from the treatment
• The team are currently investigating a new ‘off the shelf’ cell therapy that uses donor cells, which would reduce cost and improve patient outcomes

MRC improving outcomes for cancer patients

Anti-cancer treatments across the world

• University of Southampton developed anti-cancer monoclonal antibodies. The most advanced are two used to treat leukaemias such as Chronic Lymphocytic Leukemia (CLL) and Follicular Lymphoma (FL) called Ofatumumab and Obinutuzumab
• The patented research was collaboratively developed and licensed to a Swedish biotech firm, resulting in a clinical trial programme that led to a £73 million commercial agreement
• MRC funding has supported this field of research since the 1970s when scientists at the MRC LMB discovered monoclonal antibodies and later developed humanised monoclonal antibodies in the 1990s for which they won Nobel prizes

Trial improves prostate cancer patient health and care

• Research led by the Universities of Oxford and Bristol has changed the way that men with early-stage prostate cancer are diagnosed and treated
• The ProtecT trial compared active monitoring with more invasive treatments, radiotherapy and surgery, finding that patients who did not undergo invasive treatment had the same high survival rates
• The trial also found that the negative impacts of radiotherapy and surgery on urinary and sexual function persist much longer than previously thought – for up to 12 years
• Evidence has changed health policy and clinical practice through updated guidelines and optimised treatment
• MRC funding has supported the underpinning work carried out at the University of Bristol through the MRC ConDuCT-II Hub since 2014

MRC supporting healthy ageing

Preventing falls in older people

• Falls are a significant concern for older people and come at a cost of more than £2.3 billion per year to the NHS
• Home adaptation services – such as stairlifts, grab-rails and ramps – are available for those who want to continue living in their home. However, until now, there has been no evidence to demonstrate their effectiveness
• Researchers from the MRC-funded Health Data Research UK have created a dataset that shows these adaptations can help prevent falls and also identifies those most at risk of falling. The research could help inform policy for proactive interventions

Identifying genetic risk of Alzheimer’s disease

• An international study has identified 75 genes associated with an increased risk of developing Alzheimer’s disease, including 42 new genes that had not previously been implicated
• Researchers at the MRC-funded UK Dementia Research Institute analysed the genomes of 111,326 people diagnosed with Alzheimer’s disease and 677,633 genomes from healthy people, making it the largest genetic study of Alzheimer’s disease to date
• The development of a new genetic risk score could be used when recruiting patients for clinical trials aimed at treating the early stages of the disease, when damage to the brain is minimal

Brain inflammation with microglia that fail to clear debris, causing astrocytes to react. Credit: National Institute on Aging, National Institutes of Health

MRC informing health policy

Big data to improve care and outcomes for millions of people with cardiovascular disease

• UCL researchers used large-scale patient data to shape national and international clinical guidelines for the prevention, diagnosis, and treatment of a range of cardiovascular diseases. This has benefitted care and improved outcomes for millions of patients worldwide
• Evidence from the research informed a major change in guidelines, to lower the blood pressure threshold which defines hypertension, making diagnosis more accurate
• MRC funding has contributed to this research since 2012

Understanding the transmission and control of COVID-19

• Research from Imperial College London and Oxford University provided key data which underpinned recommendations and policies during the COVID-19 pandemic. This included school closure policy, social gatherings and contributed to the recommendation of interventions to protect those living in large households
• The evidence transformed our understanding of the epidemiology of COVID-19 and the measures required to protect public health
• MRC Centre for Global Infectious Disease Analysis (GIDA) scientists have tailored their research focus to COVID-19 to provide rapid, open access, real-time modelling and assessment analysis targeted at the needs of policymakers
• Since its establishment in 2008, MRC GIDA scientists provided insight into previous outbreaks of Ebola and Zika and worked with public health agencies and policy makers to improve preparedness and responses to disease outbreaks

Genome sequencing to inform outbreak response

• Researchers at the University of Birmingham developed rapid whole genomic sequencing methods to transform the management of infectious disease around the world
• The research has improved identification of transmission pathways, evolution of pathogens and sites of persistence. MRC funding supported the team to apply rapid genome sequencing to pathogens such as Ebola, Zika and SARS-COV-2
• In addition, MRC-funded research at the University of Oxford was crucial in the development of the MinION sequence platform – a ‘pocket sequencer’ that enables rapid analysis of data in the field – and the creation of spin-out company Oxford Nanopore Technologies

MRC improving health globally

Protecting human health from infectious disease in low-resource settings.

• Research from the University of Brighton has contributed to reducing human health risk from diseases including cholera, ebola, typhoid, and childhood diarrhoea in regions of Africa, Asia, and South America
• The Brighton team helped the National Institute of Cholera and Enteric Diseases to prioritise effective public health interventions in urban slum districts in India (home to 100,000 people) and the Kenyan Medical Research Institute to protect 1,170 rural inhabitants
• This research was supported by MRC in 2017 in a project which quantified routes of microbial contamination between livestock and drinking water

Improving treatment of meningitis in developing countries

• Cryptococcal Meningitis is a major cause of HIV-related deaths in developing countries, accounting for more than 180,000 deaths per year. Previous treatments involved costly medications and regular monitoring in hospitals
• Researchers at the University of Oxford, Liverpool School of Tropical Medicine, London School of Hygiene and Tropical Medicine and St. Georges, University of London demonstrated the efficacy of low-cost antifungal drug flucytosine. The WHO implemented the findings into their guidelines, which reduced costs, improved access, and led to reductions in mortality
• MRC-funded research supported key clinical trials to determine the optimum combinations of flucytosine, providing the evidence needed for implementing these guidelines
• The findings also led to a $20 million investment from global health organisation UNITAID, benefiting seven African countries

Our mission is to improve human health through world-class medical research. To achieve this, we support research across the biomedical spectrum, from fundamental lab-based science to clinical trials, and in all major disease areas. We work closely with the NHS and the UK health departments to deliver our mission, and give a high priority to research that is likely to make a real difference to clinical practice and the health of the population. Together, we:

• encourage and support research to improve human health
• produce skilled researchers
• advance and disseminate knowledge and technology to improve the quality of life and economic competitiveness of the UK
• promote dialogue with the public about medical research

Further information

Explore more impacts arising from MRC-funded research

Find out more about MRC

NIHR Oxford Biomedical Research Centre

Enabling translational research through partnership

The NIHR Oxford Biomedical Research Centre is a collaboration between the University of Oxford and Oxford University Hospitals NHS Foundation Trust to fund medical research See NIHR Oxford BRC impact

Find out about our governance

Latest News

Our Research Themes

Cardiovascular Medicine

Digital Health from Hospital to Home

Gene and Cell Therapy

Genomic Medicine

Inflammation across Tissues

Life-saving Vaccines

Metabolic Experimental Medicine

Modernising Medical Microbiology and Big Infection Diagnostics

Musculoskeletal

Preventive Neurology

Respiratory Medicine

Surgical Innovation, Technology and Evaluation

Translational Data Science

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Patient and Public Involvement

Working with patients, carers and members of the public is a vital part of the Oxford Biomedical Research Centre. We involve patients and the public in deciding what research to do, how to do it and what is done with the results. Learn more

Join the AgeX Trial Public Advisory Group

Listed 06 September 2024

Input for PPI and plain English section for a research proposal to Blood Cancer UK

Listed 05 September 2024

LAAOS-4 PPI review request

Listed 29 August 2024

Palliative care Patient and Public Involvement (PPI) pool

Listed 19 August 2024

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Keep informed about the work of the Oxford BRC by subscribing to our Mailchimp e-newsletter. It is produced several times a year and delivers news and information about upcoming events straight to your inbox.

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Biomedical Research Centres

NIHR’s 20 Biomedical Research Centres (BRCs) are networks of experts that work collaboratively between NHS trusts and internationally renowned universities. They facilitate early stage experimental medicine research and support the translation of scientific discoveries.

What are the NIHR Biomedical Research Centres?

NIHR Biomedical Research Centres (BRCs) bring together academics and clinicians to translate early scientific breakthroughs into potential new treatments, diagnostics and health technologies. 

The NIHR has awarded nearly £800m in funding to facilities across England, creating an environment where experimental medicine can thrive. 

BRCs attract the best scientists and produce world-leading research, improving patients’ lives, and contributing to the local and national economy. Their high-quality, innovative research also attracts significant investment from external funders, furthering the nation’s economic growth.

Watch how the NIHR Biomedical Research Centres are transforming patients' lives.

Where are the NIHR BRCs located?

BRCs are based within the NHS trusts hosting them and the collaborating universities. The 20 BRCs are:

• NIHR Barts Biomedical Research Centre
• NIHR Birmingham Biomedical Research Centre
• NIHR Bristol Biomedical Research Centre
• NIHR Cambridge Biomedical Research Centre
• NIHR Exeter Biomedical Research Centre 
• NIHR Great Ormond Street Hospital Biomedical Research Centre
• NIHR Imperial Biomedical Research Centre
• NIHR Leeds Biomedical Research Centre
• NIHR Leicester Biomedical Research Centre
• NIHR Manchester Biomedical Research Centre
• NIHR Maudsley Biomedical Research Centre
• NIHR Moorfields Biomedical Research Centre
• NIHR Newcastle Biomedical Research Centre
• NIHR Nottingham Biomedical Research Centre
• NIHR Oxford Biomedical Research Centre
• NIHR Oxford Health Biomedical Research Centre
• NIHR The Royal Marsden Biomedical Research Centre
• NIHR Sheffield Biomedical Research Centre
• NIHR Southampton Biomedical Research Centre
• NIHR University College London Hospitals Biomedical Research Centre  

What are the BRC themes?

Each BRC provides expertise across a broad range of health and disease areas. Their work is structured around a number of cross-cutting themes, including:

• Multimorbidity
• Data and digital health
• Precision medicine
• Rare diseases

The BRCs make use of their host organisation’s facilities, as well as other NIHR infrastructure such as NIHR Clinical Research Facilities, to conduct innovative research.

NIHR Translational Research Collaborations are hosted by BRCs, which collaborate with charity partners to develop and deliver early-phase translational research at scale. These collaborations convene UK-wide expertise in specific research areas addressing a gap or unmet need, serving as a platform to support emerging priorities in the research landscape and to co-ordinate efforts in early phase research. 

Several BRCs support the work of the NIHR BioResource , which provides a national infrastructure for volunteers to be consented and recalled for research based on their genotype and phenotype, supporting human health research and its transformation into medical practice.

How do BRCs support research?

The BRCs receive sustained funding from NIHR to translate promising scientific breakthroughs and develop them into new treatments, diagnostics and medical technologies for the benefit of patients, the public and the health and care system. BRCs support research by:

• creating an environment where scientific endeavour can thrive, attracting the foremost talent and producing world-class outputs
• supporting a critical mass of people and infrastructure focused on biomedical innovation and early translational and experimental medicine research
• supporting capacity building through Early Career Fellowships and training/development opportunities
• delivering NIHR-funded research, while working with other public funders, charities and the life sciences industry
• leveraging and attracting funding from external organisations to undertake experimental medicine and early translational research while forming key strategic partnerships

BRC support for the life sciences industry

BRCs are designed to accelerate the translation of preclinical studies from experimental to early-phase research. They are skilled at overcoming bottlenecks and moving breakthroughs along the research pipeline.

For the life sciences industry, BRCs can provide:

• collaboration between globally recognised academic researchers, specialised NHS clinicians, the life sciences industry and other BRCs
• world-class laboratory and research facilities
• bespoke specialised equipment, such as sleep clinics, PET scanners, and simulation suites
• access to large and diverse patient populations
• access to tissue samples and health data through the NIHR BioResource testbed for translational research

They will also provide project management support for every stage of a study, including:

• care pathway and health economic analysis to identify unmet clinical needs
• protocol design, including patient-and-public involvement from the first stage of protocol development
• oversight of early phase studies across all specialties

The life sciences industry and sponsors of commercial research should contact the NIHR industry team to discuss their requirements and explore which facility would be best suited to support them.

Contact the Industry team

Visit our ‘ Offer to the Life Sciences Industry ’ page to discover the full range of support available to commercial research sponsors developing and delivering research in the UK.

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The Medical Research Council (MRC) is a national funding agency dedicated to improving human health by supporting research across the entire spectrum of medical sciences, in universities and hospitals, in MRC units, centres and institutes in the UK, and in MRC units in Africa.

The Medical Research Council is a publicly funded organisation dedicated to improving human health.

We support research across the entire spectrum of medical sciences, in universities and hospitals, in our own units, centres and institutes in the UK, and in our units in Africa.

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Cambridge Institute for Medical Research

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A genome-wide CRISPR/Cas9 screen identifies calreticulin as a selective repressor of ATF6α

Nuclear proteasomes buffer cytoplasmic proteins during autophagy 1 compromise

Atlastin-1 regulates endosomal tubulation and lysosomal proteolysis in human cortical neurons

VAMP2 regulates phase separation of α-synuclein

Substrate recruitment via eIF2γ enhances catalytic efficiency of a holophosphatase that terminates the integrated stress response

Functional validation of EIF2AK4 (GCN2) missense variants associated with pulmonary arterial hypertension

p37 regulates VCP/p97 shuttling and functions in the nucleus and cytosol

Reversible assembly and disassembly of V-ATPase during the lysosome regeneration cycle

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Reaching Research 2024

• Intranet (CIMR only)

CIMR’s mission is to determine the molecular mechanisms of disease in order to advance human health.

Cimr research advances.

The endoplasmic reticulum (ER) constitutes the major cellular compartment for the synthesis, folding, and quality control of secretory proteins. An imbalance between synthesis and folding can lead to...

Autophagy is a pathway conserved from yeast to humans enabling the degradation of cytoplasmic proteins and organelles. After such substrates are captured by autophagosomes, these are trafficked to...

Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative conditions characterised by distal axonal degeneration of the corticospinal tract axons. Mutation of the ATL1 gene is one...

While both, vesicle-associated membrane protein 2 (VAMP2) and α -synuclein have been extensively studied, this study reveals a novel, unexpected role for their interaction. α-synuclein is a small...

Protein phosphorylation activates important biological processes that are later deactivated by dephosphorylation. Phosphoserine/threonine dephosphorylation is catalyzed by holophosphatases comprising...

Pulmonary arterial hypertension (PAH) is a disorder in which aberrant vascular remodelling raises pressures in the pulmonary vasculature, causing right heart failure. Affected young adults often...

A new paper from the Rubinsztein lab, led by Lidia Wrobel, describes how mutations in the AAA+-ATPase valosin-containing protein (VCP; also called p97 or Cdc48), can contribute to diseases such as...

Lysosomes function as the terminal degradative compartment of a cell’s endocytic and autophagic pathways, and as a multifunctional signalling hub integrating the cell’s response to nutrient status...

Latest news

Outback Outreach!

19 August 2024

Members of the Deane lab have taken outreach to new heights - or should that be distances! – by joining in with a school science week in Australia. The team made a fun video for the children at St...

1 August 2024

Last week CIMR hosted an on-line event, held over three mornings, for sixth form students looking to pursue careers in medicine or biomedical sciences. Students heard talks from scientists at all...

CIMR & MBU host students on the Aspiring Scientists Training Programme

12 July 2024

We have had a great week with a group of sixth-form students taking part in the Gurdon Institute's ASTP programme . As a widening participation scheme, the programme is targets young people who may...

View all news

New CIMR publications

Buss lab (Nature Communications 2024)

Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor.

Ron lab (eLife 2024)

Rubinsztein lab (Nature Cell Biology 2024)

Nuclear proteasomes buffer cytoplasmic proteins during autophagy compromise

Reid lab (Neurobiology of Disease 2024)

Lautenschlager lab (Nature Cell Biology 2024)

VAMP2 chaperones α-synuclein in synaptic vesicle co-condensates

Ron lab (PNAS 2024)

Marciniak lab (Human Molecular Genetics 2024)

Functional validation of EIF2AK4 (GCN2) missense variants associated with pulmonary arterial hypertension | Human Molecular Genetics | Oxford Academic (oup.com)  

Reiner Schulte (contributor, Springer Protocols 2024) 

Practicalities of Cell Sorting

Rubinsztein lab (Science Advances 2024)

Luzio lab (Molecular Biology of the Cell 2024)

Robinson lab (Journal of Cell Biology 2024)

The role of the AP-1 adaptor complex in outgoing and incoming membrane traffic

Marciniak lab, in collaboration with Prof Rintoul (Royal Papworth Hospital) & Matthew Garnett (Sanger Institute) (European Respiratory Journal 2024)

Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs  in vitro  models of mesothelioma

Weekes lab (Cell Host & Microbe 2024)

Human cytomegalovirus degrades DMXL1 to inhibit autophagy, lysosomal acidification, and viral assembly

Loss of WIPI4 in neurodegeneration causes autophagy-independent ferroptosis  

p300 nucleocytoplasmic shuttling underlies mTORC1 hyperactivation in Hutchinson–Gilford progeria syndrome

Ron lab (The EMBO Journal, 2023) The IRE1β-mediated unfolded protein response is repressed by the chaperone AGR2 in mucin producing cells

Weekes lab (Nature Communications, 2023) Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection

Salje lab (mSphere, 2023) Orientia tsutsugamushi: comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium | mSphere (asm.org)  

Woods lab (Journal of Medical Genetics, 2023) Evidence of a genetic background predisposing to complex regional pain syndrome type 1

Rayner/ Deane labs (Nature Communications, 2023) The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family

Rubinsztein lab (Developmental Cell, 2023) Mammalian autophagosomes form from finger-like phagophores

Warren lab in a collaboration co-led with the Nangalia lab [Wellcome Sanger Institute; Cambridge Stem Cell Institute] and Kent lab [University of York] (Nature Communications, 2023) Convergent somatic evolution commences in utero in a germline ribosomopathy 

Weekes lab (Cell Reports, 2023) Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity

Weekes lab in collaboration with Gewurz lab [Harvard Medical School] (Molecular Cell, 2023) An Epstein-Barr virus protein interaction map reveals NLRP3 inflammasome evasion via MAVS UFMylation

Griffiths lab (Science, 2023) Ectocytosis renders T cell receptor signaling self-limiting at the immune synapse

Rubinsztein lab (Neuron, 2023) Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration

Deane lab (PNAS, 2023) Altered plasma membrane abundance of the sulfatide-binding protein NF155 links glycosphingolipid imbalances to demyelination

Warren lab (Nucleic Acid Res., 2023) Cryo-EM reconstruction of the human 40S ribosomal subunit at 2.15 Å resolution

Gershlick lab (J. Cell Biology, 2023) The exocyst complex is an essential component of the mammalian constitutive secretory pathway

Read lab (Acta Crystallographica Section D, 2023) Likelihood-based docking of models into cryo-EM maps

Ron lab in collaboration with Elisa De Franco and Andrew Hattersley [University of Exeter] (EMBO Mol. Med 2023) Infancy-onset diabetes caused by de-regulated AMPyla tion of the human endoplasmic reticulum chaperone BiP

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Postal Address: CIMR, The Keith Peters Building, Hills Road, Cambridge, CB2 0XY

Information provided by: [email protected]

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The MRC Centre for Environment and Health undertakes the highest quality research in the fields of environment and health, to inform health policy and the understanding of key issues affecting our society. The Centre achieves this by bringing together the best researchers from all areas of public health, encouraging novel cross-disciplinary approaches, and by providing the highest quality training to new and existing researchers in these fields. The Centre is based upon the principles of openness, transparency, inclusivity and integrity in all its work, with the primary goal of improving national and international public health and protecting the future generations.

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Improving medical research in the United Kingdom

Stephen h. bradley.

1 Leeds Institute of Health Sciences, University of Leeds, Worsley Building, Leeds, LS2 9JT UK

Nicholas J. DeVito

2 The DataLab and Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, New Radcliffe House, 2nd floor, Radcliffe Observatory Quarter,Woodstock Road, Oxford, OX2 6GG UK

Kelly E. Lloyd

Patricia logullo.

3 UK EQUATOR Centre, Centre for Statistics in Medicine, NDORMS, University of Oxford, Windmill Road, Oxford, OX3 7LD UK

Jessica E. Butler

4 Centre for Health Data Science, University of Aberdeen, Aberdeen, AB25 2ZD UK

Associated Data

Not applicable.

Poor quality medical research causes serious harms by misleading healthcare professionals and policymakers, decreasing trust in science and medicine, and wasting public funds. Here we outline underlying problems including insufficient transparency, dysfunctional incentives, and reporting biases. We make the following recommendations to address these problems: Journals and funders should ensure authors fulfil their obligation to share detailed study protocols, analytical code, and (as far as possible) research data. Funders and journals should incentivise uptake of registered reports and establish funding pathways which integrate evaluation of funding proposals with initial peer review of registered reports. A mandatory national register of interests for all those who are involved in medical research in the UK should be established, with an expectation that individuals maintain the accuracy of their declarations and regularly update them. Funders and institutions should stop using metrics such as citations and journal’s impact factor to assess research and researchers and instead evaluate based on quality, reproducibility, and societal value. Employers and non-academic training programmes for health professionals (clinicians hired for patient care, not to do research) should not select based on number of research publications. Promotions based on publication should be restricted to those hired to do research.

Introduction

The UK invests substantial sums in medical research and the international reputation of the sector is vital to the government’s industrial strategy [ 1 ]. Unfortunately, systemic problems undermine the rigour of medical research and lead to costly research waste [ 2 ].

In this commentary, we propose straightforward measures to reduce waste in medical research that will safeguard investments and ensure the UK remains a productive setting for researchers committed to genuine scientific discovery.

What are the causes of the reproducibility crisis in medical research?

While fraud is an important problem that leads to non-reproducible research, many of the issues that undermine reproducibility do not involve deliberate misconduct [ 3 , 4 ]. Here, we concentrate on identifying and suggesting remedies to the systemic threats to research rigour and reproducibility.

Lack of transparency for methods and data

Although most UK medical research is funded through taxation and charitable donations, there are remarkably few requirements placed on researchers to share data, adequately describe methods, or provide their full results. Understanding exactly how studies were carried out requires full transparency of study methods and analytic code (where applicable) to verify results and conclusions, ideally with full access to the data. Without providing this information, the validity of published results can only be taken on trust.

Some journals now have policies requiring authors to make their data, analytic code, and protocols available. In practice, these requirements are routinely ignored [ 5 – 7 ]. Considerations of patient privacy or commercial confidentiality are not insurmountable barriers to adequate transparency. Research participants should be offered the opportunity to consent to the sharing of their data, or data can be de-identified and provided via third-party, securely-managed access. The OpenSafely project has provided a successful model throughout the COVID-19 pandemic for safe and secure access to UK patient records for emergency epidemiological research [ 8 ]. While individual electronic health records cannot be shared in this instance, the OpenSafely project has made transparency into data access, code, and analysis plans central to the project. The Vivli platform provides another model for securely sharing data collected from clinical research studies and numerous platforms exist for sharing non-sensitive data [ 9 ].

Consistent and mandatory sharing of data, code, and protocols via journals is one route to improved transparency. However, there is a strong case that all study documentation for publicly funded research should be reported in the public realm at study completion (regardless of article publication status). The establishment of a single national repository would provide a much more complete and useful record of experiments, as well as reduce duplication in reporting requirements that researchers currently face. The Health Research Authority has recently announced plans for all clinical trials to be automatically registered following ethical approval, in partnership with the ISRCTN registry [ 10 ]. This infrastructure could form the nucleus of a more ambitious research repository, hosting comprehensive documentation for all study types.

Proposed measure 1 Journals and funders should ensure authors fulfil their obligation to share study protocols and, as far as possible, analytical code and research data regardless of the study’s ultimate publication status in a journal.

Reporting and publication biases

It is well established that results which are ‘positive’ or novel are much more likely to be published [ 11 ] leading to a distorted public record. One study found that 96% of research findings were ‘statistically significant’, a mathematical impossibility [ 12 ]. Where unpublished results are taken into account, the evidence of benefit for interventions may diminish or disappear altogether [ 11 , 13 ].

We can monitor whether clinical trials have been published because of legal and ethical requirements that clinical trials are registered prior to commencement [ 14 ]. However, clinical trials are a minority of all medical studies. For other study types, including observational studies that have informed healthcare decision-making throughout the coronavirus pandemic, there is little expectation that researchers pre-register their analysis plans and hypotheses. This makes it impossible to monitor what research is planned, if research plans have been followed, if all results are published, and if interpretation involves unscientific “spin” (Table) [ 15 ]. Pre-registering study plans for any research type is now straightforward and free to researchers [ 16 , 17 ]. Requiring pre-registration for medical research can and should be used to promote transparency and accountability.

Although we believe pre-registration enhances transparency and should be more widely used, even when research is pre-registered, it is common to find unacknowledged deviations between the proposed research and the published manuscript [ 6 ]. While registration makes these deviations detectable, detection is onerous and journals often fail to take action when alerted to these issues [ 6 ]. Related ‘questionable research practices’, like manipulating analyses to generate statistically significant results (‘p-hacking’) and amending study hypotheses retrospectively to suit the results found (Hypothesising After the Result is Known, or ‘HARKing’) can lead to biased findings when research is not pre-registered or the registrations are not checked against final reports [ 18 ].

Registered reports are a publishing format with two methods for preventing these poor research practices. In a registered report, reviewers assess methods before data collection begins. When the researchers and reviewers agree that the design is appropriate, the researchers are given in-principle approval for publication, regardless of the study findings, as long as the proposed methodology is adhered to [ 19 ].

Promoting publishing via registered reports addresses both outcome reporting and publication biases for almost all types of research [ 19 ]. Since journals decide on publication based on the methods before the results are known, researchers have less incentive to strain to produce eye-catching or positive results. Instead, methodologically sound research enters the record without bias regarding what those results might say. Early evidence suggests that registered reports do improve the quality and rigor of proposed study designs [ 20 , 21 ]. Unfortunately, medicine lags behind other disciplines like psychology in adopting registered reports, with just over 1% of medical journals offering the format in 2020 [ 22 ].

Funders should either incentivise publication via registered report, which will increase their uptake by more journals, or establish their own publication platforms which prioritise the registered report format. The NIHR and Wellcome Trust have both established open and peer-reviewed publication platforms for their funded research [ 23 , 24 ]. Novel funding pathways are demonstrating that it is possible to integrate peer reviews for registered reports in grant applications which could improve the efficiency of academic discovery and dissemination [ 25 , 26 ].

Proposed measure 2 Funders and medical journals should incentivise the uptake of registered reports.

Lack of transparency on conflicts of interest

Researchers potential conflicts of interest are difficult to ascertain. Conflict of interest statements in publications are brief and often omit important conflicts, even major financial conflicts like sources of funding or relationships with industry [ 27 ]. The RetractionWatch project has logged numerous instances of problematic findings, and eventual retractions of articles, due to important undisclosed conflicts of interest [ 28 ]. In the UK, there are currently voluntary registers for those who have received payments from the pharmaceutical industry and for doctors [ 29 , 30 ]. However, because there is little incentive for individuals to make such declarations, these registers are greatly underutilised. Only 0.002% of doctors’ registered with the General Medical Council (GMC) were listed on the doctors’ voluntary register in 2020 [ 31 ]. Patients, the public and other scientists are entitled to be able to check whether a researcher has a conflict of interest and to understand what potential biases might impact a study.

There have been calls for the GMC to curate a registry of doctors’ interests [ 32 , 33 ]. While such a register would mark an important advance in transparency, it would not cover non-medically qualified researchers. Therefore the UK’s research regulator, the Health Research Authority (HRA), along with the GMC, could be tasked with creating a central register, similar to the US OpenPayments database, to index all medical researchers’ interests using the unique identity numbers (ORCiD) which are already required by institutions and funders [ 34 , 35 ] Expectations of accurate and up-to-date declarations could be encouraged by employers during researchers’ appraisals, although a legal mandate for regulators to ask for such declarations may require legislation [ 36 ].

Proposed measure 3 a mandatory national register of interests for all those who are involved in medical research in the UK should be established, with an expectation that individuals maintain the accuracy of their declarations.

Dysfunctional incentives and research culture

Decisions about who to hire, fund and promote in academia are often informed using reductive, simple metrics such as citations, the journal impact factor of publications or grant income [ 37 , 38 ]. Such metrics perversely incentivise researchers to generate a high quantity of publications which are perceived to be exciting or newsworthy, rather than prioritising high quality reproducible research that actually benefits patients and the public. Practices that support high quality research by improving transparency and reducing bias, such as registering studies and publishing all results, are not typically used to appraise performance in academia [ 39 ]. Initiatives which seek to mitigate dysfunctional incentives and promote practices that are conducive to reproducible research are becoming more widely established throughout the UK. These include the UK Reproducibility Network (UKRN), the San Francisco Declaration on Research Assessment (DORA), Résumé for Researchers, and the Concordat to Support the Career Development of Researchers [ 40 – 44 ]. Such efforts should be supported and expanded.

Proposed measure 4 funders and institutions should stop using metrics such as citations and journal’s impact factor to assess research and instead evaluate based on quality, reproducibility and societal value.

Some clinical professionals are incentivised to undertake research because publication is used as a selection criteria for training programmes and for professional promotion [ 45 ]. Such dysfunctional incentives promote research that is undertaken solely for career advancement, by individuals who may lack methodological expertise and commitment to produce high-quality reproducible research. There is no persuasive evidence that authoring scientific publications improves the clinical performance of healthcare professionals. Instead we should aspire to create a system of medical research that produces “less research, better research, and research done for the right reasons” [ 46 ].

Proposed measure 5 employers and training programmes for health professionals should remove incentives to publish from their selection procedures.

In this commentary we have set out recommendations to improve the transparency and reproducibility of medical research. Not all of these would be easily implemented, and further evidence is needed to articulate their value and best practice. Moreover sincere engagement from funders, government, journals, researchers, and their employing institutions is required. Elsewhere, we highlighted three actions that warrant prioritisation as readily implementable measures with high potential for impact [ 22 , 47 ]. These are:

• Mandatory registration of interests for all people and institutions who conduct and publish health research on a single on-line platform accessible to all;
• Prioritisation by journals and funders of publication of research via Registered Reports; and.
• Public pre-registration before data collection of the study design of all publicly-funded medical research, along with protocols, analytic code and, where possible, research data and results.

Table ​ Table1 1 outlines how these actions, along with other proposed measures outlined in this commentary could address some of the problems in medical research.

Problems in medical research and how they can be mitigated by authors’ proposed strategy

There is growing acknowledgement that systemic problems pervade health research. But as long as we fail to take action, medicine’s reproducibility crisis will persist. The recommendations in this commentary aim to advance beyond identification of the problems to meaningful, achievable reform.

Acknowledgements

David Mellor (Center for Open Science) contributed to the written evidence submitted to the parliamentary select committee inquiry on reproducibility and research integrity on which this commentary is based. We would also like to thank Till Bruckner (TranspariMED) for feedback provided on that submission.

Abbreviations

Author contributions

SHB authored the first draft of the paper, NJD, KEL, PL and JEB contributed to subsequent revisions of the text. All authors read and approved the final manuscript.

Availability of data and materials

Declarations.

Stephen Bradley: I am employed as a General Practitioner for one day a week. I receive funding for PhD study from CanTest collaborative (Cancer Research UK, C8640/A23385). The publication costs of a collection of essays on health inequalities which I co-edited for the Fabian Society was funded by the Association of the British Pharmaceutical Industry and Lloyds Pharmacies, I received no direct funding or payment for this. I sit on the NIHR’s Health Services & Delivery research prioritisation committee (unpaid aside from reimbursement of travel expenses). I am a co-investigator on a study which is funded by Yorkshire Cancer Research (Patient-centred models for surveillance and support of cancer survivors with bowel and breast cancer). I am a member of the steering group of a campaign to improve health research (the Declaration to Improve Health Research). I have previously received funding from the Mason Medical Foundation to undertake a study on chest x-ray and lung cancer diagnosis.

Nicholas DeVito: I am a doctoral student at the DataLab (soon to be the Bennett Institute for Applied Data Science supported by the Peter Bennett Foundation) and the Centre for Evidence-Based Medicine at the University of Oxford and I am supported in my studies by a studentship from the Naji Foundation. I have been employed on grants in the last three years from the Laura and John Arnold Foundation, the Good Thinking Society, and the German Federal Ministry of Education and Research (BMBF). I have also received grant support from the Fetzer Franklin Memorial Fund.

Kelly Lloyd: I am supported by an Economic and Social Research Council studentship [grant number ES/P000745/1]. I am a member of a steering group of a campaign to improve health research (the declaration to improve health research). Patricia Logullo: I am a postdoctoral meta-researcher at the University of Oxford and a member of the UK EQUATOR Centre, an organisation that promotes the use of reporting guidelines, and I am personally involved in the development of some new reporting guidelines or their extensions. I receive funding from Cancer Research UK and NIHR Biomedical Research Centre for my research work. I am also a member of the Oxford-Brazil EBM Alliance, a not-for-profit organisation interested in disseminating evidence-based medicine principles (unpaid).

Jessica Butler: I am employed by the University of Aberdeen where I currently receive funding for medical research from the Health Foundation and from Wellcome Trust. I am an honorary analyst for NHS Grampian (unpaid). I am on the editorial board of Scientific Reports and Scientific Data (unpaid). I am a member of the UK Reproducibility Network and the Association of Professional Healthcare Analysts.

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Contributor Information

Stephen H. Bradley, Email: ku.ca.sdeel@arbsdem .

Nicholas J. DeVito, Email: [email protected] .

Kelly E. Lloyd, Email: ku.ca.sdeel@lekmu .

Patricia Logullo, Email: [email protected] .

Jessica E. Butler, Email: ku.ca.ndba@reltubacissej .

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Dipesh Patel’s journey from TB patient to research advocate

Tuberculosis (TB) remains one of the most stigmatized diseases globally, often associated with misconceptions and fears that can lead to isolation and shame for those affected. Despite advances in medical treatment, the social stigma surrounding TB continues to be a significant barrier to diagnosis, treatment, and support for patients.

According to a World Health Organization (WHO) report , TB is the second leading infectious killer worldwide, after COVID-19, surpassing even HIV and AIDS. In 2022, an estimated 10.6 million people, including 5.8 million men, 3.5 million women, and 1.3 million children, fell ill with TB globally. Despite its prevalence, TB is still seen as a disease associated with shame and backwardness, effecting people physically, mentally, emotionally, and financially.

Among the struggling TB patients was Dipesh Patel, a young 27 year old man of Gujarati Indian descent from Leicester, diagnosed in July 2015.

 At the time, he was 18 years old and in his final year of college. His diagnosis came as a shock, not only because TB seemed like a disease of the past but also because it came with the added burden of stigma.

Physically, the disease left him weak and frail, resulting in significant weight loss. He was admitted to Leicester Royal Infirmary, where his treatment lasted for nine months. During this time, he faced a challenging treatment regimen that caused liver complications, requiring adjustments, and ultimately prolonging his recovery. Even simple tasks, like picking up a cup of water, became monumental efforts. Dipesh described TB as debilitating, “It was really strange when you sort of lose that connection with your body in a way. It won’t do what it’s told.”

The long-term hospitalization was a significant challenge for him, particularly as it was his first extended stay away from home. He adapted to the routine of hospital life, but the experience was isolating and difficult, especially for someone so young.

The social stigma associated with TB affected Dipesh, though within his Gujarati Indian community was somewhat understood due to its prevalence. Nonetheless, he initially kept his diagnosis private, only informing close friends and family, when necessary due to the stigma.

After his recovery, Dipesh chose to turn his experience into something positive by participating in the EVENT TB research study investigating how the immune system responds to TB. By volunteering, he contributed to advancements in TB diagnosis and treatment, recognizing the importance of such research for public health and society. His participation also provided him with reassurance, knowing that his health was being closely monitored through the study. As Dipesh put it, “What was initially a very negative, maybe devastating traumatic event, you know, you’re putting it to good use to further whatever research needs doing.”

His experience of both having TB and witnessing a loved one struggle with the same disease deepened his understanding of the critical need for awareness and prevention. To further this cause, he volunteered to participate in a film for an art installation focused on the stigma surrounding TB. This project allowed him to share his story and help raise awareness about the challenges TB patients face, particularly the social stigma that can accompany the disease.

Dipesh’s participation in the EVENT study was valuable for society because it helped researchers better understand the immune response in TB patients, which is crucial for developing more effective ways to identify and treat those at risk of progressing from latent TB infection to active TB disease. His involvement contributed to advancements that could lead to more targeted and effective TB prevention and treatment strategies.

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The McGill AMR Centre hosted its 4th Annual Symposium on Monday June 3rd and welcomed over 120 people to this in-person event.  Thank you to all who joined the conversation on the Genomics and Evolution of AMR.  With 13 flash talks, 47 posters and a “Career Insight” lunch with 6 non-academic guest experts, trainees also had a highly interactive and stimulating day!

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• Patricia Fontela, Pediatrics, McGill University " Antibiotic use in the critical care setting: a quest for balance"
• Jesse Shapiro, Microbiology & Immunology, McGill University "Interactions between antibiotics, phages, and pathogens within cholera patients"
• Christian Landry, Biology, Université Laval "Studying the evolution of antifungal resistance at high-resolution"

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• Adam Belley, Senior Director, Clinical Microbiology, Venatorx Pharmaceuticals Inc.
• Jessica Blavignac, Director, Medical & Scientific Affairs, bioMérieux Canada Inc.
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