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Immune-mediated inflammatory diseases: understanding common mechanisms

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Summary

The Medical Research Council (MRC) is issuing a call for research projects into immune-mediated inflammatory diseases (IMIDs). It is anticipated that multiple awards of up to £200,000 (funders’ contribution) will be available for up to 24 months. Funding is available for exploratory or hypothesis-driven research that will systematically identify or explore common disease mechanisms across multiple IMIDs. We encourage applications from cross-disciplinary and cross-institutional teams to develop research in this important field.

This is a two stage call; an Expression of Interest stage will be assessed in October 2018, and full applications invited forward for assessment in March 2019.

Background

Immune-mediated inflammatory diseases (IMIDs) of non-infectious disease origin represent a subpopulation of multimorbid conditions, they affect specific or multiple organs and often share both immunological and mechanistic features. The prevalence and incidence of IMIDs are both increasing by around 5% per annum, representing significant challenges for individuals, carers and the health and social care system.

Understanding common mechanisms of disease pathology, complex interactions of different IMIDs and the underlying loss of immune tolerance or early instigators of the inflammatory cascade are urgently needed to develop efficient strategies for IMID prevention, early diagnosis and to design and deliver better interventions for patients.

A recent workshop, co-organised by the MRC, JDRF, ARUK and Wellcome outlined some of the research gaps and priorities in this area. The workshop highlighted that, while there is evidence for disease associations, progress is being limited by research being pursued in a disease-specific manner, according to clinical presentation, and often being focused on latter stages of disease. Consequently, some of the broader learnings around the early mechanisms surrounding loss of immune tolerance or early inflammatory instigators may have been overlooked. It is therefore important to identify and explore common disease mechanisms together with the underlying causal pathways. This work will help feed into a wider funders’ initiative on multimorbidity within the UK health and social care research landscape.

The outcomes of the projects supported through this funding initiative will identify areas where future research can have the most impact and will build the foundation for mechanistic studies to unravel underpinnings of various IMIDs, causal effects of shared risk factors and disease interactions. The eventual goal of the research should lead to better preventative and therapeutic approaches and policies to manage multiple conditions, taking into account patient perspectives of living with and managing IMIDs, as well as those of their families and carers.

The call has been developed to catalyse IMID research by supporting both hypothesis-driven and exploratory studies that, in addition to classical epidemiological methods, would utilise new approaches to complex data collection and analysis of datasets originating from multiple sources.

We are particularly keen to support applications from cross-disciplinary and cross-institutional teams involving clinicians, epidemiologists, data scientists, social and behavioural scientists, and basic biomedical researchers to tackle the complexity of IMIDs at all levels. Additionally, we are keen to build capacity in this area of research, therefore applications from early-stage career researchers are particularly welcomed.

The awards will offer up to £200,000 support for projects lasting between one and two years (up to a maximum duration of 24 months). These may be used to generate data that would provide a strong evidence base and clear rationale for larger programmes of research. Alternatively, they may support methodological research or explore the underlying basis of IMIDs using model systems and mechanistic approaches. In addition, these awards may support tools or resources which have the potential to provide benefit to the wider IMID community.

This call is part of a longer-term effort to address the challenge of multimorbidity, find solutions for the UK health and social care sector, and improve the quality of life and health outcomes for people with multimorbidities.

Call objectives and remit

The call aims to provide funds to support mechanistic studies using existing infrastructure and data sources including established cohorts, surveys, biobanks, and primary and secondary care data to:

  • identify new mechanisms which are shared across multiple IMIDs
  • evaluate the environmental impact on genetic predisposition to IMIDs
  • investigate immunololgical tolerance within IMIDs
  • explore the interplay between microbiota and IMIDs
  • examine the organ specificity of some IMIDs. 

We will consider applications that will contribute to building the evidence base for more focused research on specific types of IMIDs or will generate data to enable larger-scale experimental medicine and stratified medicine studies. Awards are expected to help establish new and galvanise existing research collaborations between clinical and academic experts from different research fields.

The scope of the call includes, but is not limited to the following research topics:

  • IMID clustering in defined population/patient groups
  • addressing prevalence and changes in IMIDs during the life course (such as in childhood, during pregnancy or postpartum period)
  • biomedical drivers of IMIDs
  • shared mechanistic pathways in IMIDs
  • IMID biomarkers, early predictors and genetic associations
  • innovative methodological approaches, tools and technologies for capturing and measuring patients' complexities in the context of IMIDs
  • enriching data for established population and clinical cohorts.

Assessment process

All proposals will be assessed by a MRC panel of experts and will go through an Expression of Interest stage (September/October 2018). Applicants will be contacted via email shortly after the panel meeting, to inform them of the panel’s decision and the feedback on their application. Applicants, whose proposals would be deemed competitive for funding through this call will subsequently be invited to submit a full proposal through Je-S for consideration by the funding panel in March 2019.

Expression of Interest stage applicants should consider carefully the following criteria, which will be taken into account by the expert review panel when assessing proposals:

  • potential of the outcomes of the proposed research to lead to significant new insights into IMIDs. Through, for example, providing insight into underlying mechanisms in IMIDs, generating new hypotheses for further mechanistic studies or identifying novel ways to capture and monitor IMIDs.
  • level of innovation and novelty associated with the proposal
  • quality of the research team and potential of the proposed collaboration to stimulate high-quality research
  • availability of resources – existing links with the major data sources or evidence of negotiated data access
  • appropriateness of requested resources and the effectiveness of the proposed data management structure and plans, and the value for money offered by the proposed research.

Who can apply?

The following may apply:

  • those eligible for standard MRC research grants as described in the guidance for applicants
  • MRC unit/institute staff.

All investigators (PI & Co-Is) are required to have a verified Je-S account. Please note that opening a Je-S account can take some time, so applicants should start the process as soon as possible. Applicants with an industrial partner(s) will need to submit an MRC Industry Collaboration Award (MICA) Form and Heads of Terms as part of their Je-S application. Please refer to the guidance on MICAs.

Expression of Interest forms must be submitted no later than 16:00 on 28 September 2018. Forms must be emailed to: imid@mrc.ukri.org

Funding available

Up to £1 million is available for this call. Research proposals will be funded on the basis of 80% of the full economic cost (except for exceptional costs, which are funded at 100% - see the guidance for applicants), with the funders’ contribution (described as 'RC contribution' within Je-S) not exceeding £200,000. The MRC expects applications to demonstrate the maximum research impact from funding.

Contacts

Applicants may wish to discuss the suitability of their proposal for the remit of the call, or other questions related to the scientific aspects of their application, by sending a query to imid@mrc.ukri.org

To discuss your eligibility or any other non-scientific queries please contact our Research Funding Policy and Delivery Team: RFPD@headoffice.mrc.ac.uk

Queries relating to Je-S should be directed to the Je-S Helpdesk.