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ME/CFS highlight notice

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and serious debilitating medical condition with a diverse range of symptoms. Profound physical and/or mental fatigue is the most well-known manifestation, while others include pain, disturbed sleep patterns and gastrointestinal problems. Each patient experiences their own personal combination of symptoms but certain ones dominate.

Building our portfolio of ME/CFS research has been a high priority for the MRC for a number of years. In 2020, the Medical Research Council (MRC) and the National Institute for Health Research (NIHR) jointly funded the £3.2m DecodeME study, which is the world’s largest genome-wide association study (GWAS) of ME/CFS and aims to identify genetic differences that may indicate underlying causes or increased risk of developing the condition. In 2011, MRC made available £1.5m through a call for proposals for new research into the mechanisms of ME/CFS.

This highlight notice seeks to encourage high-quality response-mode funding applications to any of MRC’s Research Boards. Some areas previously identified as important and tractable for research by the MRC ME/CFS Expert Group were not well covered in applications funded through the 2011 call; these are highlighted below and our Research Boards would particularly welcome applications in these areas.

Research proposals – application and assessment process

Through this highlight notice, applicants are invited to submit innovative research proposals that address the mechanisms underlying chronic changes related to ME/CFS in one or more of the areas shown below:

  • Immune dysregulation: There is evidence for a disturbance in innate and adaptive immunity in ME/CFS including alterations in cytokine profile, absolute and functional alterations in T cells and NK cells and occurrence of autoantibodies and allergic reactions that may explain some of the manifestations such as fatigue and flu-like symptoms. A number of infectious and environmental exposures have been associated as triggering these changes.
  • Pain: Headache, facial pain and myalgia are reported symptoms of ME/CFS that may involve altered sensory and/or cognitive processing in the relevant neural pathways.
  • Improved sub-phenotyping and stratification of ME/CFS: ME/CFS is often considered a broad spectrum disorder or syndrome and, as in other disease areas, it may be that the causes and mechanisms underpinning diverse symptom profiles are different. Better patient phenotyping and stratification could provide valuable new insights into the natural history of the disease and enable the development of more effective, better targeted treatments.
  • Mechanisms of ME/CFS in children: The manifestations of ME/CFS in children represent a major clinical management challenge. There is a need for research aimed at improving understanding of the mechanisms that lead to the early onset of the disease; this knowledge can then be used for the development and evaluation of new treatment options, as a prelude to their assessment in large-scale clinical trials.
  • Neuropathology: There is now preliminary evidence supporting the view that inflammatory mechanisms in the brain and spinal cord may underlie the pathophysiology of some severe disease ME/CFS phenotypes. The availability of biobanks creates a unique opportunity for interrogation.

Applications should seek to improve mechanistic understanding in these areas through the study of cross-disease symptomatology, and pathways, in the clinic and/or laboratory.

Additionally, this highlight notice aims to build on the success of the 2011 call in increasing capacity in ME/CFS research and address the need for multidisciplinary teams to tackle the significant research challenges in this area.

Proposals submitted under this highlight notice should, therefore, involve partnerships between ME/CFS researchers and established, leading investigators working in relevant areas, but who are new to the ME/CFS field. It is expected that those investigators who are new to ME/CFS research will make a substantial contribution to the programme of work, to enable them to build their own track record in ME/CFS research.

When outlining the skill sets of the investigator group, applicants should highlight which investigator(s) are new to the ME/CFS field and how their experience and expertise will add to the UK ME/CFS research base.

MRC encourages (but does not require) applicants to work in partnership with other funders where appropriate. Depending on the programme of work to be undertaken, applicants may wish to seek cash or in-kind support from charitable and/or industrial partners; details of support from any project partners should be included on the Je-S application form and in the case for support.

Applicants will be required to attach a letter of support from any project partner(s) to their application.

This is a cross-Board highlight notice and proposals may be submitted to any of the MRC’s Research Boards as appropriate based on scientific or clinical area. All applications received under this highlight notice will be assessed through MRC’s standard assessment procedure.

General guidance on how to apply for funding from the MRC can be found in the Applicants’ Handbook. (PDF, 1.04MB)

Potential applicants are advised to contact Dr Joanna Robinson if they are considering submitting an application under this highlight notice, and all applicants are requested to reference this highlight in the ‘Objectives’ and the ‘Case for Support’ sections of their proposals. Unfortunately, the MRC is not able to broker new research partnerships on the part of applicants as we do not have the resources to do this.


Dr Joanna Robinson, Head of Population and Systems Medicine

Email: joanna.robinson@mrc.ukri.org

Dr Sherie Wright, Programme Manager

Email: Sherie.Wright@mrc.ukri.org