MRC Precision Prevention — Biological Mechanisms of Response Variation 2026: Invited Applications Up to £5 Million, Closing 5 November

MRC Precision Prevention — Biological Mechanisms of Response Variation 2026: Invited Applications Up to £5 Million, Closing 5 November

Prevention works, on average. That average is the problem this call is built around.

Statins, vaccines, weight-management drugs, immunological interventions — each one has a population-level effect size that hides enormous individual variation. Some people get most of the risk reduction. Some get very little. Some get the adverse effects without the benefit. The Medical Research Council’s position in this funding opportunity is blunt: the biological mechanistic pathways underpinning that variation are poorly understood, and relying on average effects across diverse populations produces suboptimal benefit, unnecessary treatment, and persistent health inequalities.

So MRC is putting £15 million behind human experimental studies designed to interrogate those pathways directly — not to infer them from observational data, but to perturb a biological system in people and measure what happens. The mandatory expression of interest (EOI) stage for this 2026 call closed on 17 September 2026. UKRI has since opened the invited full application stage: it runs from 10 September to 5 November 2026, and only teams invited after the EOI can apply. The current listing is therefore useful to those invited teams; the earlier EOI is no longer accepting submissions.

Key details

The two published windows overlapped: the invited full application stage opened on 10 September, while the EOI stage closed on 17 September. That does not make the EOI optional. At this point, a new EOI cannot be submitted; a team may proceed only if UKRI invited it after a successful EOI. UKRI’s current full-stage page is the authoritative place for the application questions and updated terms.

What MRC is actually funding

The scope statement sets two non-negotiable conditions. Your project must include an experimental intervention or challenge in humans, and it must focus on a mechanistic hypothesis. Everything else follows from those two sentences.

The framing is the shift from treatment to prevention in the 10-year NHS health plan for England. MRC connects that policy shift to a research gap: heterogeneity is commonly observed in response, risk reduction, adverse effects, and clinical outcomes associated with biomedical interventions, and nobody can currently explain most of it at a mechanistic level. The call asks for interventional studies in humans that validate a mechanistic hypothesis and directly interrogate the biology governing two things — the transition from health to early disease, and the variation in how people respond to biomedical prevention interventions.

The method MRC wants is deliberately specified: experimental challenges, interventions, or controlled perturbations, with measurable outcomes that provide evidence of the pathways involved. The contrast drawn in the call is with inferring pathways from observational data. If your design cannot perturb the system and observe the response, it is likely out of scope.

Four illustrative themes are listed, and MRC is explicit that they are non-exhaustive:

• Improving mechanistic understanding of how interventions modify biological pathways across different population groups, enabling more personalised and equitable prevention and avoiding harm.
• Generating mechanistic insights into early disease pathways that can support future development and tailoring of novel precision prevention approaches, and support stratification of populations.
• Using current treatment interventions as mechanistic tools to understand pathways influencing responsiveness to prevention interventions, informing stratified prevention.
• Validating surrogate endpoints that reflect the biological mechanisms underlying heterogeneity in response and track the health-to-disease transition — explicitly flagged as something that should not be the primary focus of an application.

Two areas get a named welcome: gaps in understanding biological mechanisms in multiple long-term conditions and in metabolic disease, and, where relevant, work in underrepresented populations.

What is out of scope — read this before you write anything

This call has an unusually long exclusion list, and most rejected applications will fail here rather than on quality. MRC will not support:

• Characterisation or phenotyping work aiming to elucidate disease aetiology, where that is the main aim and there is no experimental challenge or prevention intervention context.
• Experimental intervention or challenge in animals.
• Biomarker discovery projects. Exploratory biomarker studies are separately stated to be ineligible.
• Projects where the primary mechanistic question is about managing established disease rather than preventing onset — that is, tertiary prevention.
• Pre-clinical model development and validation.
• Development and evaluation of novel therapeutics, diagnostics, or devices (routed instead to UKRI Translation: MRC proof of concept).
• High-throughput screening approaches to target validation.
• Late-phase clinical efficacy trials (routed to MRC and the NIHR Efficacy and Mechanism Evaluation Programme).
• Observational studies involving no experimental challenge.

MRC points the first group of these towards its applicant-led schemes — the MRC research grant, new investigator research grant, and partnership grant — which is a useful signal. If your idea fits better there, it will not be rescued by reframing it for this call.

There is also a separate list of costs MRC will not fund at all: clinical studies designed to assess the safety or efficacy of treatments, PhD studentship costs, publication costs, and funding used as a bridge between grants.

Who can apply, and the demand management rules

The opportunity is open to organisations with standard UKRI eligibility. To apply you must be employed by an eligible research organisation and be able to show that you will direct the project and be actively engaged in the work.

For applicants without a contract of employment covering the full project, submitting an application constitutes a commitment by the research organisation that, if successful, contracts will be extended beyond the project end date and all necessary support will be provided — including mentorship and career development for early career researchers. That is a real institutional undertaking, not a formality, and your research office needs to see it early.

Demand management applies, and the rule is specific: a research organisation may lead or partner on more than one application, and applications may involve more than one organisation, but an individual may be project lead on only one application. There is no limit on the number of applications on which you can be a project co-lead. If two groups in your department are circling the same idea, resolve who leads before the Funding Service submission.

Businesses and charity or third sector organisations cannot supply the project lead or a project co-lead, but can participate as project partners on an application led by an eligible UK organisation.

Because MRC is a lead funder here, international researchers can join as “project co-lead (international)”. Their intellectual contribution and added value must be clearly explained and justified in the Applicant and team capability to deliver section. Other international collaborators, and UK partners not at approved organisations, should be included as project partners.

The money, and how full economic costing shapes your budget

The total pot is £15 million. A single project can request up to £5 million full economic cost. MRC funds 80% of FEC and 100% of permitted exceptions; the maximum MRC contribution, including exceptions, is £4 million. These are different ceilings: a budget may reach £5 million FEC, but the MRC contribution cannot exceed its stated maximum. Set the full cost and the requested contribution out clearly with your finance team.

Eligible cost headings include a contribution to the salary of the project lead and co-leads, research and technical staff posts, research consumables, equipment, travel, data preservation, data sharing and dissemination, estates and indirect costs, and public partnerships including payments to public contributors.

Costs for work at international organisations by international project co-leads are funded at 100%. There is a cap: the total requested for international applicants from high income countries (those not on the OECD DAC list of ODA recipients), plus India and China, must not exceed 30% of the total resources requested. There is no cap on costs for applicants from DAC-listed development assistance countries. If your mechanistic work depends on a cohort or facility in, say, the United States or Germany, model that 30% ceiling into the budget from the start rather than discovering it at costing stage.

The two-stage process and what each stage is really for

Stage one — expression of interest (closed). The EOI was mandatory and had to be submitted through UKRI’s precision prevention survey by 17 September 2026 at 4:00pm UK time. This stage is closed. Applicants who did not submit an EOI cannot enter the current full application round.

MRC said information provided at EOI would not be formally assessed. It was used to check remit and fit to scope, anticipate submission levels, and inform peer review and panel composition and membership. In the event of high demand, MRC reserved the right to introduce shortlisting at that stage.

For anyone who submitted an EOI, that distinction explains why the stage still mattered: UKRI used it for remit, planning and reviewer selection, with a possible shortlist if demand was high. For current applicants, the practical consequence is simpler: only those invited after the EOI may continue, and the full proposal is the competitive assessment.

Stage two — invited full application. The full stage opened on 10 September 2026 and closes on 5 November 2026 at 4:00pm UK time. It runs through the UKRI Funding Service; Je-S is not accepted. The project lead completes the application, team members and partners contribute, and only the lead research organisation can submit. Confirm account access and your research office’s internal timetable immediately. UKRI says an application cannot be changed after submission and may be rejected if it does not follow the opportunity guidance.

The current full-stage guidance specifies independent expert review, a possible shortlisting step, a 14-calendar-day applicant response to reviewer comments, and a panel that scores and prioritises applications. The panel meeting is expected on 24 and 25 February 2027, subject to confirmation. MRC makes the final decision; applicants are to be informed within 10 working days of the funding decision meeting, with feedback within eight weeks.

Milestones: a structural requirement, not a formatting detail

MRC states that experimental medicine awards will typically carry at least two milestones with defined success criteria, reflecting timely progression points and allowing mechanistic hypotheses to be laid out and assessed as the project moves forward. Milestones exist to mitigate risk and to make genuinely high-risk, innovative projects fundable.

At full application stage, provide at least two key progression milestones. UKRI asks these to divide the work into costed phases with clear go/no-go decisions, target and acceptable thresholds, and distinct sequential timepoints. Give realistic timelines for regulatory steps, team and participant recruitment, study completion, and analysis. Success criteria should be specific, measurable, achievable, relevant and timely. The application gives a 1,500-word limit for the milestones response.

The strongest piece of advice in the whole call is a single line: it is advisable to structure the project so that the critical questions are addressed as early as possible in the plan. A five-year design that only tests its central mechanistic hypothesis in year four is asking a panel to accept four years of unfalsifiable risk. Front-load the falsification.

How to prepare a competitive application

Name the gap, then name the consequence. Successful projects should address a clearly articulated gap in understanding either the mechanisms behind variation in response to preventive interventions or the biology of the health-to-early-disease transition — and have a clear pathway to informing the targeting, timing, or optimisation of precision prevention. Two moves, not one. A beautiful mechanistic question with no line to targeting or timing will read as basic science in the wrong competition.

Specify the readout before you specify the intervention. In all cases, relevant validated biological readouts must be measured to test the proposed mechanistic hypothesis. If your readout is not validated, you have a biomarker discovery project — which is ineligible.

Pick an intervention with an established safety profile. The call names pharmacological or immunological challenges as examples. A novel agent drags you into therapeutic development, which is out of scope and routed elsewhere.

Stay in the pre-disease window. Projects must focus on the pre-disease state, early stage, or emergence of disease. The moment your population is people with established disease being managed, you are in tertiary prevention and outside remit.

Address effectiveness, efficiency, and equity explicitly. MRC asks you to demonstrate how the insights could enhance all three, including by identifying opportunities to tailor interventions to the high-risk people and populations most likely to benefit. The equity dimension is not decoration here; it is tied to the call’s stated rationale about persistent health inequalities.

Engage your research office and regulators early. For costings and application writing, MRC’s guidance is to contact your research office first, allowing sufficient time for internal review and submission. For human research in the NHS, public health or social care, check whether a Schedule of Events Cost Attribution Tool (SoECAT) is needed. If required, contact an AcoRD specialist, complete the online SoECAT, obtain authorisation, then include the authorised funder-export spreadsheet in the Human participation section. Regulatory approvals are milestones in their own right.

Build the Funding Service responses from the live questions. The current form asks for a plain-English summary (up to 550 words), keywords, vision, intervention, approach, project milestones, team capability, and partner support where applicable, alongside questions on human participation and other relevant areas. The intervention response should explain its biomedical nature and established safety profile. The approach should provide a detailed plan and timeline, such as an embedded Gantt chart. At least two non-overlapping milestones need costed phases and decision criteria. Follow the current field-specific word limits and criteria in the Funding Service rather than relying on an older draft or on this overview.

Get partner documentation right. Each named project partner must provide a letter or email of support, combined into a single PDF. UKRI does not require an industry partner simply because this is an experimental medicine call; an industry partner is only relevant where your design calls for one. Core team members, and organisations employing core team members, cannot also be project partners. Ask your research office to check roles and letters before submission.

Common mistakes to avoid

• Submitting an observational study with an experimental veneer. No challenge or perturbation means no eligibility.
• Assuming the EOI is still open or that an uninvited team can submit a full application. The EOI closed, and stage two is restricted to teams UKRI invited after it.
• Two colleagues each leading an application. You may lead only one.
• Building an international budget above the 30% ceiling for high income countries, India, and China.
• Making surrogate endpoint validation the centrepiece. The call permits it as a component and explicitly says it should not be the primary focus.
• Assuming Je-S. The full stage runs on the UKRI Funding Service and your organisation must be registered.
• Requesting ineligible costs — studentships, publication costs, or bridge funding — and forcing a costing rework late.

Frequently asked questions

Can I submit an expression of interest now? No. The EOI closed on 17 September 2026. The current full application stage is limited to teams invited after their EOI.

Will my EOI have been scored? UKRI’s EOI guidance said responses would not be formally assessed. They informed remit checks, demand estimates and reviewer and panel composition; UKRI also reserved the right to shortlist at EOI stage in the event of high demand.

Can I be involved in more than one application? Yes, as a project co-lead on any number. As project lead, only one.

Can a company or charity lead? No. They can participate as project partners on an application led by an eligible UK organisation.

Can an overseas researcher be funded? Yes, as project co-lead (international), at 100% of eligible costs, subject to the 30% cap for high income countries, India, and China.

How long can the project run? Between three and five years.

What will assessors consider? The current guidance lists vision and fit to the call, the intervention, team capability (including effective industry partnership where relevant), ethical and responsible research, and requested resources. It also assesses the approach, project plan and milestones, methodology and experimental design, reproducibility and statistical design, risk management, research environment, patient and public involvement, communication and engagement, and data management and sharing.

Is there guidance beyond the written call? Yes — MRC has published a recorded video for potential applicants covering the opportunity and frequently asked questions, linked from the Additional information section of the official page.

Official links and contacts

• Current invited full application page: Invite only: Precision prevention: biological mechanisms of response variation
• Earlier EOI page (closed): Expression of interest: Precision prevention
• Opportunity-specific queries: [email protected]
• General MRC funding and policy queries: [email protected]
• UKRI Funding Service helpdesk: [email protected], 01793 547490 (Monday to Thursday 8:30am–5:00pm, Friday 8:30am–4:30pm)

Sensitive information — a declaration of interest, a conflict for UKRI to consider in reviewer selection, unavailability due to parental leave, or the fact that an application is an invited resubmission — should go to [email protected] with the funding opportunity title and “sensitive information” in the subject line, rather than into the application body.

Next steps

If your team submitted an EOI and has received an invitation, check the current call page and complete the application in the UKRI Funding Service. Coordinate early with your research office, finance team, partners, and any AcoRD/SoECAT support your study needs. If you did not receive an invitation, you cannot apply in this round. International co-leads may be eligible where they make the required intellectual contribution, and organisations outside the approved list can participate as partners under the call rules.

For invited teams, the current submission deadline is 5 November 2026 at 4:00pm UK time. The EOI date of 17 September 2026 has passed and cannot be used as the live deadline; it remains relevant only to explain why access to this full stage is restricted.