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Understanding the Mechanisms of CFS/ME

This call is now closed for applications and is available for reference purposes only. Details of funded proposals can be found here.

 

MRC invites proposals for high-quality, internationally competitive research partnerships addressing Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Collaborative proposals must be submitted via Je-S by 4pm on 7 June 2011.

Context

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) 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, while others include pain, disturbed sleep patterns and gastrointestinal problems. Each patient experiences their own personal combination of symptoms.

 

CFS/ME research has been a high priority area for the MRC for some time. The development of this call for proposals has been informed by the work of the MRC Expert Group, (chaired by Professor Stephen Holgate), other experts in the field of CFS/ME and research leaders in aligned areas who have identified and prioritised medical research topics where the MRC might target efforts to encourage and support high-quality proposals.

 

Details of MRC’s past activities related to CFS/ME research, including the development of research topics for this call for proposals, can be found on: http://www.mrc.ac.uk/Ourresearch/ResearchInitiatives/CFSME/index.htm

Focus of the call

CFS/ME is a complex, heterogeneous condition that comprises the interaction of different biological, physical and psychological mechanisms. Understanding these mechanistic pathways and the interactions between them is important in improving understanding of the condition.

 

The focus of this initiative is to support high-quality, innovative medical research that increases the current knowledge base of CFS/ME; and on drawing in expertise and resources from related research fields. Applications must address the mechanisms underlying chronic changes related to CFS/ME, particularly focusing on one or more of the following areas:

 

Autonomic dysfunction: In CFS/ME evidence supports an association between the condition and various forms of hypotension, reduced heart rate variability, alterations in the hypothalamic-pituitary-adrenal axis and sympathetic stress response systems.
Cognitive symptoms: Cognitive problems are commonly reported in CFS/ME. These include impaired short-term working memory and thinking, difficulties with concentration and attention span, and impaired information processing.
Fatigue: Chronic disabling fatigue is a common, poorly understood phenomenon. There is a need to better understand the measurement and mechanisms of central (brain) and peripheral (muscle) fatigue and post-exertional malaise as well as the influence of complicating factors such as depression, sleep disorders and pain.
Immune dysregulation: There is evidence for a disturbance in innate and adaptive immunity in CFS/ME 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 CFS/ME that may involve altered sensory and/or cognitive processing in the relevant neural pathways.
Sleep disorders: Disordered sleep is a characteristic symptom in CFS/ME including, impaired daily sleep/wake rhythms and disrupted sleep, hypersomnia, insomnia, and secondary problems such as restless legs syndrome.

 

Applications should seek to understand these mechanisms through the study of cross-disease symptomology, and pathways, in the clinic and/or laboratory. Additionally, this initiative aims to address the current lack of capacity in CFS/ME research, and the need for multidisciplinary teams to tackle the significant research challenges in this area. Proposals submitted to this call must therefore involve partnerships between CFS/ME researchers and established, leading investigators working in relevant areas, but who are new to the CFS/ME field. It is expected that those investigators who are new to CFS/ME research will make a substantial contribution to the programme of work, to enable them to build their own track record in CFS/ME research. The capacity building aspect of the call is focused on bringing new established investigators into CFS/ME research; therefore, applicants may not request PhD studentships as part of this call.

 

Available funds

Up to £1.5M is available to support research proposals submitted against this call. Subject to the submission of proposals of sufficient research quality, it is anticipated that between 2 and 4 awards will be made.

Eligibility criteria

This call follows standard RCUK eligibility criteria and is open to UK-based researchers, working in partnerships, who can show they will direct the proposed research and be actively engaged in carrying it through. Joint proposals from people in the same or different institutions including non-academic organisations are expected, but one person will be identified as the lead contact for review and administration purposes and is known as the Principal Investigator.

 

Eligible institutions include UK higher education institutions, Research Council institutes, and eligible Independent Research Organisations (IROs). All IROs listed on the RCUK web page are eligible to apply.

How to apply

Proposals submitted against this call must be costed using the Full Economic Costing (FEC) model. You should submit your proposal using the Research Councils’ Joint electronic Submission (Je-S) System (https://je-s.rcuk.ac.uk/). Guidance on setting up a Je-S account and on filling out the Je-S forms can be found at: https://je-s.rcuk.ac.uk/jesHandbook/jhHome.aspx.

 

When adding a new proposal, you should select Council ‘MRC’, document type ‘Standard Proposal’ and the ‘Strategic’ Scheme. On the Project Details page you should select the ‘CFS/ME Research Initiative’ Call. Details of which Research Organisations have registered to use Je-S are available from http://www.so.stfc.ac.uk/jes/jes1/RODetails(Web).pdf.

 

Note that clicking ‘submit document’ on your proposal form in Je-S initially submits the proposal to your host organisation’s administration, not to the MRC. Please ensure you allow sufficient time for your organisation’s submission process between submitting your proposal to them and the call closing date. The MRC must receive your application by 4pm on 7 June 2011.

 

You must submit the following items:

  • Case for Support – further guidance on completing your case for support can be found below
  • CV for each named researcher
  • Justification of Resources
  • Pathways to Impact – guidance from RCUK on completing your Pathways to Impact statement can be found at:
  • http://www.rcuk.ac.uk/kei/impacts/Pages/home.aspx

 

Additionally, you may include a cover letter, any letters of support and/or an Exceptional Costs pro forma if applicable.

Case for support

Applicants must prepare a case for support (maximum 8 pages A4) as part of their application.

 

Your case for support should contain the following sections, if appropriate:

  • 1. Title
  • 2. Importance of the research
  • 3. Scientific potential
    • People and track record – this section should include details of which investigator(s) are new to CFS/ME research and how their expertise is relevant to research in this area.
    • Research environment
    • Research plans – in addition to detailed research plans, this section should outline the investigators’ approach to their partnership and clearly indicate which investigator(s) will carry out each aspect of the proposed programme of work.
  • 4. Ethics and research governance
  • 5. Data preservation for sharing
  • 6. Dissemination - plans for dissemination to potential academic beneficiaries should be included here; details of plans for public engagement, exploitation of results and/or dissemination to potential non-academic beneficiaries should be included in your ‘pathways to impact’ statement.
  •  

    General guidance on preparing your case for support can be found in the MRC Applicants Handbook. Your case for support should indicate how the proposed programme of work meets the aims of the call, particularly outlining what contribution the research will make to increasing understanding of chronic changes related to CFS/ME and how the investigators will work in partnership to deliver the objectives of the proposed work. Additionally, when outlining the skill sets of the investigator group, applicants should highlight which investigator(s) are new to the CFS/ME field and how their experience and expertise will add to the UK CFS/ME 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.

    Application assessment

    Applications will be assessed by expert peer-review and applicants will be given the chance to respond to reviewers’ comments. Applications will be prioritised for funding by a panel Chaired by Professor Stephen Holgate which will largely comprise Members from across MRC’s Research Boards (PSMB, NMHB, MCMB and IIB) based on their areas of expertise. Funding decisions will be made by the MRC Population and Systems Medicine Board.

     

    The following general criteria will be used in the assessment of applications:

  • 1. Research quality;
  • 2. Impact - importance, innovation and timeliness of the research and its likely contribution to the CFS/ME research knowledge base;
  • 3. Productivity;
  • 4. Fit to the call:
    • Does the proposed work address one or more of the identified priority research areas?
    • Does the investigator group include one or more researchers who are new to CFS/ME research? Do they have the appropriate skills and expertise to make a positive contribution to the CFS/ME research base in the UK? Is the partnership likely to help build capacity in CFS/ME research in the UK?

    Timetable

    The key dates are listed below:

    Task

    Date

    Launch call

    22 February 2011

    Submission deadline

    7 June 2011

    Peer review (external)

    June 2011 – September 2011

    Applicants’ response

    October 2011

    Prioritisation Panel meeting

    November 2011

    Applicants receive notification of outcome

    November 2011

    Awards announced

    December 2011

    This page will be updated with the date of the Prioritisation Panel meeting when it has been confirmed. Applicants will receive notification of the outcome of their proposal shortly after the Prioritisation Panel has met.

    If you have a query about the call, contact MRCCalls@ssc.rcuk.ac.uk

     

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