Expression of interest: Precision prevention: biological mechanisms of response variation

Expression of interest: Precision prevention: biological mechanisms of response variation is sponsored by Medical Research Council (MRC). Expression of interest: Precision prevention: biological mechanisms of response variation.

Expression of interest: Precision prevention: biological mechanisms of response variation – UKRI Funding opportunity: Expression of interest: Precision prevention: biological mechanisms of response variation Medical Research Council (MRC) 17 September 2026 4:00pm UK time 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.

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 submit a mandatory expression of interest (EOI) and be invited to submit a full application.

This funding opportunity is open to organisations with standard eligibility. Check if your organisation is eligible .

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 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: charity and third sector organisations International researchers As the Medical Research Council (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 should be clearly explained and justified in the application, see Applicant and team capability to deliver. Read the UKRI project co-lead (international) eligibility for more details.

Please contact us if you are uncertain about eligibility. Find contacts in the ‘contact details’ section. 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: support for people with caring responsibilities alternative working patterns UKRI can offer disability and accessibility support for UK Research and Innovation (UKRI) applicants and grant holders during the application and assessment process. Demand management is being applied to this funding opportunity. Further details are provided in the ‘Who can apply’ section.

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 the following (non-exhaustive): 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 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 MRC: new investigator research 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. The duration of this award can be between three and five years. 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. The total budget for this funding opportunity is £15 million. The FEC of your project can be up to £5 million.

MRC will fund 80% of the FEC and 100% of permitted exceptions. Find out more about full economic costing .

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 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.

clinical studies designed to assess the safety or efficacy of treatments costs for PhD studentships funding to use as a ‘bridge’ between grants 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 necessary. Our TR&I Principles set out UKRI’s expectations of organisations funded by UKRI in relation to due diligence for international collaboration.

As such, applicants for UKRI funding may be asked to demonstrate how their proposed projects will comply with our approach and expectation towards TR&I, identifying potential risks and the relevant controls you will put in place to help proportionately reduce these risks. See further guidance and information about TR&I , including where you can find additional support.

Stage one: expression of interest We are running a mandatory expression of interest (EOI) stage. You must submit an EOI by 17 September 2026. You must submit your EOI by completing the expression of interest precision prevention survey .

Stage two: full application We are running the full funding opportunity on the new UK Research and Innovation (UKRI) Funding Service so please ensure that your organisation is registered. You cannot apply on the Joint Electronic Submissions (Je-S) system. We will publish full details on how to apply when the funding opportunity opens.

The full funding opportunity will open on 10 September 2026 and close on 5 November 2026. The Medical Research Council (MRC), as part of UKRI, will need to collect some personal information to manage your Funding Service account and the registration of your funding applications. We will handle personal data in line with UK data protection legislation and manage it securely.

For more information, including how to exercise your rights, read our privacy notice . If you or a core team member need to tell us something you wish to remain confidential, email PPexpmed@mrc. ukri.

org Include in the subject line: [the funding opportunity title; sensitive information].

Typical examples of confidential information include: individual is unavailable until a certain date (for example due to parental leave) additional information about eligibility to apply that would not be appropriately shared in the ‘Applicant and team capability’ section conflict of interest for UKRI to consider in reviewer or panel participant selection the application is an invited resubmission For information about how UKRI handles personal data, read UKRI’s privacy notice .

How we will assess your application We will assess your application using the following process. Stage one: expression of interest Information provided as part of the expression of interest will not be formally assessed.

We will use this information to: check remit and fit to funding opportunity scope anticipate expected submission levels inform peer review and panel composition and membership In the event of high demand for this funding opportunity, we reserve the right to introduce shortlisting at this stage. Stage two: full application We will assess your application using the following process.

We will invite peer review experts to review your application against the criteria and a panel will rank it alongside other applications, after which they will make a funding recommendation. The Medical Research Council (MRC) will make the final funding decision. Find out more about MRC’s assessment process .

We reserve the right to modify the assessment process as needed. We support the San Francisco declaration on research assessment and recognise the relationship between research assessment and research integrity. Find out about the UKRI principles of assessment and decision making .

Using generative artificial intelligence (AI) in expert review Generative AI may be used only for the purpose of language refinement during application assessment.

When using generative AI to refine the language of a review, expert reviewers and panellists must ensure that: no part of the application being assessed is entered into a generative AI tool no personal information from the application is disclosed generative AI is not tasked with understanding, summarising or evaluating the application’s content Expert reviewers and panellists must also: comply with relevant intellectual property and data protection legislation not take into account or speculate within their assessment whether generative AI has been used to develop the application For more detail see our policy on the use of generative AI .

The full criteria for assessment will be published when the full application funding opportunity opens. Get help with your application If you have a question and the answers aren’t provided on this page. The helpdesk is committed to helping users of the UK Research and Innovation (UKRI) Funding Service as effectively and as quickly as possible.

In order to manage cases at peak volume times, the helpdesk will triage and prioritise those queries with an imminent opportunity deadline or a technical issue.

Enquiries raised where information is available on the Funding finder opportunity page and should be understood early in the application process (for example, regarding eligibility, content or remit of a funding opportunity) will not constitute a priority case and will be addressed as soon as possible.

For help and advice on costings and writing your application please contact your research office in the first instance, allowing sufficient time for your organisation’s submission process. For questions related to this specific funding opportunity please contact PPexpmed@mrc. ukri.

org Any queries regarding the system or the submission of applications through the Funding Service should be directed to the helpdesk. Email: support@funding-service. ukri.

org Our phone lines are open: Monday to Thursday 8:30am to 5:00pm To help us process queries more efficiently, we request that users highlight the council and opportunity name in the subject title of their email query, include the application reference number, and refrain from contacting more than one mailbox at a time. For further information on submitting an application read How applicants use the Funding Service .

Research and innovation impact Impact can be defined as the long-term intended or unintended effect research and innovation has on society, economy and the environment; to individuals, organisations, and the wider global population. Video for potential applicants This recording provides more information about the funding opportunity and answers frequently asked questions.

Watch the video (YouTube) Research disruption due to COVID-19 We recognise that the COVID-19 pandemic has caused major interruptions and disruptions across our communities.

We are committed to ensuring that individual applicants and their wider team, including partners and networks, are not penalised for any disruption to their career, such as: disruptive working patterns and conditions role changes that may have been caused by the pandemic Reviewers and panel members will be advised to consider the unequal impacts that COVID-19 related disruption might have had on the capability to deliver and career development of those individuals included in the application.

They will be asked to consider the capability of the applicant and their wider team to deliver the research they are proposing. Where disruptions have occurred, you can highlight this within your application if you wish, but there is no requirement to detail the specific circumstances that caused the disruption. This is the website for UKRI: our seven research councils, Research England and Innovate UK.

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