Invite only: Precision prevention: biological mechanisms of response variation

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Funding opportunity Funding opportunity: Invite only: Precision prevention: biological mechanisms of response variation Opportunity status: Open Funders: Medical Research Council (MRC) Funding type: Grant Total fund: £15,000,000 Publication date: 10 September 2026 Opening date: 10 September 2026 9:00am UK time Closing date: 5 November 2026 4:00pm UK time Start application Apply for funding to investigate why biomedical prevention interventions work differently across people. Projects must generate mechanistic evidence in humans by testing biomedical experimental interventions or challenges in pre-disease or early disease states, providing insight into how to improve the targeting and effectiveness of precision prevention strategies. Your project must: include an experimental intervention or challenge in humans focus on a mechanistic hypothesis The full economic cost (FEC) of your project can be up to £5 million over a duration of up to five years. MRC will fund 80% of your project’s full economic cost. You must have submitted a mandatory expression of interest (EOI) and be invited to submit a full application. Who can apply This opportunity is open to organisations with standard eligibility. Check if your organisation is eligible . You can only apply for this funding opportunity if we have invited you to do so following a successful expression of interest. Who is eligible to apply To be eligible to apply for this funding opportunity you must: be employed by an eligible research organisation show that you will direct the project and be actively engaged in the work be part of a team invited to apply after submitting an expression of interest For applicants who do not have a contract of employment for the duration of the proposed project, by submitting an application the research organisation is confirming, if it is successful: contracts will be extended beyond the end date of the project all necessary support for you and the project will be provided, including mentorship and career development for early career researchers A research organisation may lead or partner on more than one application and applications may comprise more than one research organisation. Individuals may be project lead on only one application. However, individuals can act as project co-leads on any number of applications. Who is not eligible to apply If you are employed by these organisations you cannot apply as project lead or project co-lead, but can participate as project partners on an application led by an eligible UK organisation: businesses charity and third sector organisations International researchers As MRC is a lead funder for this funding opportunity, international researchers can apply as ‘project co-lead (international)’. Project co-leads (international) make a major intellectual contribution to the design or conduct of the project. Their contribution and added value to the research collaboration should be clearly explained and justified in the application, using the appropriate application sections, such as ‘Applicant and team capability to deliver’. Read the UK Research and Innovation (UKRI) project co-lead (international) eligibility policy for more details. Please contact us if you are uncertain about eligibility. You should include all other international collaborators (or UK partners not based at approved organisations) as project partners. Equality, diversity and inclusion We are committed to achieving equality of opportunity for all funding applicants. We encourage applications from a diverse range of researchers. We support people to work in a way that suits their personal circumstances. This includes: career breaks support for people with caring responsibilities flexible working alternative working patterns UKRI can offer disability and accessibility support for UKRI applicants and grant holders during the application and assessment process. What we're looking for Demand management Demand management is not being applied to this funding opportunity. Scope As the UK population grows and ages, increasing rates of ill health and declining healthy life expectancy are contributing to a worrying trajectory for health outcomes. The shift to prevention from treatment as part of the 10-year NHS health plan for England has the potential to reduce the burden of multiple long-term conditions and chronic diseases, support an ageing population, tackle health inequalities, lower associated NHS costs, boost productivity and drive economic growth. Some effective prevention interventions already exist, but their impact is often limited by substantial variation in how individuals and populations respond. Heterogeneity is commonly observed in response, risk reduction, adverse effects, and clinical outcomes associated with biomedical interventions. The biological mechanistic pathways underpinning this variation are poorly understood. Current approaches typically rely on average effects across diverse populations, leading to suboptimal benefit, unnecessary treatment, and persistent health inequalities. This funding opportunity aims to support interventional studies in humans to validate a mechanistic hypothesis and directly interrogate the biological mechanisms governing the transition from health to early disease and the mechanisms underlying variation in response to biomedical prevention interventions. By deploying experimental challenges, interventions or controlled perturbations, studies can test biological mechanisms, with measurable outcomes providing evidence of the pathways involved, rather than inferring them from observational data. These mechanistic insights then inform how prevention interventions could be better targeted, timed, and delivered across different populations. These findings should contribute to an iterative feedback loop of mechanistic insight and re-testing that enables progressively more precise and effective prevention strategies. Studies may address the heterogeneity of response of existing validated prevention interventions or investigate biological mechanisms that could support the future development of novel precision prevention interventions. In all cases, relevant, validated biological readouts must be measured to test the proposed mechanistic hypothesis. Exploratory biomarker studies are not eligible for funding. Successful projects should address a clearly articulated gap in understanding the mechanisms underlying variation in response to preventive interventions or the biological mechanisms governing the transition from health to early disease. This should have a clear pathway to informing the targeting, timing, or optimisation of precision prevention approaches. Projects should demonstrate how these insights could enhance the effectiveness, efficiency, and equity of prevention, including by identifying opportunities to tailor interventions to those (high risk) people and populations most likely to benefit. Project themes could include a combination of: improving mechanistic understanding of how interventions modify biological pathways across different population groups, enabling more personalised and equitable prevention approaches and avoiding harm generating mechanistic insights into early disease pathways that can enable the future development and tailoring of novel precision prevention approaches and support the stratification of populations use of current treatment interventions as mechanistic tools to understand pathways that influence responsiveness to prevention interventions and inform stratified prevention approaches validating surrogate endpoints that reflect biological mechanisms underlying heterogeneity in response to prevention interventions and track the transition between health and disease. This should not be the primary focus of the application This list is not exhaustive. What your application must include Your application must involve an experimental investigation in humans at its core, which has been designed to validate a mechanistic hypothesis. Projects must focus on the pre-disease state, early stage or emergence of disease. This should include a biomedical intervention or challenge, with an established safety profile, such as pharmacological or immunological. We particularly welcome applications that address gaps in our understanding of biological mechanisms in multiple long-term conditions and metabolic disease and, where relevant, in underrepresented populations. Activities we do not support The activities that are ineligible for support are: characterisation or phenotyping work aiming to elucidate disease aetiology, where this is the main aim and without an experimental challenge or prevention intervention context experimental intervention or challenge in animals, using clinical assets to explore prevention and disease mechanisms and pathways biomarker discovery projects projects where the primary mechanistic question is directed at managing established disease rather than preventing its onset (tertiary prevention) pre-clinical model development and validation These activities are supported through the following MRC applicant-led funding opportunities: MRC: research grant MRC: new investigator research grant MRC: partnership grant The following activities are also ineligible for support through this funding opportunity: development and evaluation of novel therapeutics, diagnostics or devices (supported by the UKRI Translation: MRC proof of concept funding opportunity) high-throughput screening approaches to target validation late-phase clinical efficacy trials (supported by MRC) and National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme) observational studies involving no experimental challenge Learn about MRC’s remit, programmes and priority areas . Please see the ‘Additional information’ section for a video on this funding opportunity and answers to frequently asked questions. Milestones Milestones allow us to mitigate risk and support potentially high-risk, innovative projects. Experimental medicine awards will typically have at least two milestones with defined success criteria that reflect timely progression points and allow mechanistic hypotheses to be laid out and assessed as the project moves forward. As part of the invited full application stage, your milestones should also provide a realistic indication of timelines for key steps, such as regulatory steps, study team recruitment, participant recruitment, study completion and data analysis. Milestone success criteria should be SMART (specific, measurable, achievable, relevant and timely) and detail any robust go or no-go criteria. For all projects, it is advisable to structure the project so that the critical questions are addressed as early as possible in the plan. Duration Projects may last up to five years. You should clearly justify the proposed duration in relation to the scope, complexity and objectives of the work. Funding available The FEC of your project can be up to £5 million. MRC will fund 80% of the FEC and 100% of permitted exceptions. The maximum MRC contribution, including any identified exceptions funded at 100%, is £4 million. Find out more about full economic costing . What we will fund You can request funding for costs such as: a contribution to the salary of the project lead and co-leads support for other posts such as research and technical staff research consumables equipment travel costs data preservation, data sharing and dissemination costs estates and indirect costs public partnerships and related activities, including payments to public contributors You can also request costs for work to be undertaken at international organisations by international project co-leads. We will fund 100% of the eligible costs. The total of such costs requested for international applicants from high income countries (those not on the OECD DAC list of ODA recipients), India and China, must not exceed 30% of the total resources requested. There is no cap on costs requested for international applicants from development assistance countries (DAC). For more information on international costs and what we will and will not fund see costs we fund and the Collaborate with Researchers in Norway guidance . What we will not fund We will not fund: research involving randomised trials of clinical treatments costs for PhD studentships publication costs funding to use as a ‘bridge’ between grants Project partner A project partner is a collaborating organisation in the UK or overseas, including partners based in the EU, who will have an integral role in the proposed research. You may include project partners that will support your research project through cash or in-kind contributions, such as: staff time access to equipment sites or facilities the provision of data software or materials recruitment of people as research participants providing samples, such as human tissue, for the project Each project partner must provide a statement of support. If your application involves industry partners, they must provide additional information if the relationship falls within the industry collaboration framework . Find out more about subcontractors and dual roles . Who cannot be included as a project partner Any individual included in your application core team cannot also be a project partner. Any organisation that employs a member of the application core team cannot be a project partner organisation. This includes other departments within the same organisation. If you are collaborating with someone in your organisation, consider including them in the core team as project co-lead, or specialist. They cannot be a project partner. Human participation in research If you are applying to do research in the NHS, public health or social care you usually need to complete a Schedule of Events Cost Attribution Tool (SoECAT). We are looking for evidence you have taken the appropriate steps and for the full costs of your research to be appropriately attributed. It is important to complete a SoECAT to be eligible for support from the National Institute for Health Research (NIHR) Research Delivery Network. You must complete a SoECAT even if you do not think your research will involve excess treatment costs. See MRC guidance on who needs to complete a SoECAT . SoECAT guidance can be found on the NIHR website. These are the steps you need to take: Contact an attributing the costs of health and social care Research and Development (AcoRD) specialist as early as possible in the application process. Complete an online SoECAT. If you do not have an account for NIHR’s Central Portfolio Management System you will need to create and activate one. Request authorisation of your SoECAT. When you have authorisation, include the ‘funder export’ Excel document from your SoECAT as part of your application in the Human participation in health-related research section. Contact us about any issues including a SoECAT or AcoRD specialist feedback in your application, such as: your proposed research involves human participation and the NHS, but you do not think you need a SoECAT, explain why not when you contact us your proposed research involves human participation in health and social care (not NHS), and you think you need a SoECAT Find contacts in the ‘Contact details’ section. Supporting skills and talent We encourage you to follow the principles of the Concordat to Support the Career Development of Researchers and the Technician Commitment . Trusted Research and Innovation (TR&I) UK Research and Innovation (UKRI) is committed in ensuring that effective international collaboration in research and innovation takes place with integrity and within strong ethical frameworks. Trusted Research and Innovation (TR&I) is a UKRI work programme designed to help protect all those working in our thriving and collaborative international sector by enabling partnerships to be as open as possible, and as secure as

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