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Pump Priming Awards for preliminary research using IMPC knockout mice

Aims

Researchers are invited to apply for pump priming awards to support the receipt and preliminary use of gene knockout mouse lines developed and phenotyped through the International Mouse Phenotyping Consortium (IMPC)

Up to £0.5m is available through an initiative opening in April 2017, with 12-25 awards to be made in November 2017. As the awards are for preliminary studies only, they will be of 1-2 years’ duration and £20-40k in value. This is the second and final pump-priming award: the 2016 initiative made 15 awards with a mean value of £33k.

Applications are invited from UK-based research groups to receive knockout mice and undertake early biological investigations that build on existing research expertise and underpin longer-term research goals that would be supported through standard funding mechanisms.

The initiative aims to achieve the following:

  • support early up-take and biological investigations of the knockout mice to underpin future, more substantial research proposal(s) and maximise the value of MRC’s partnership investment in the IMPC
  • focus the UK academic research community’s attention on the importance of using well-validated, comprehensively-phenotyped mouse knockout lines, as available through the IMPC and the MRC Mary Lyon Centre
  • highlight the IMPC resource as a means of minimizing duplication of mouse knockout work, thereby reducing the number of animals used in model development.

Background to this investment

The International Mouse Phenotyping Consortium (IMPC) and the Mary Lyon Centre (MLC)

The IMPC is an international partnership between 18 research institutes and 5 international funders that aims to deliver broad-based phenotyping of knock-out (KO) mice for each of their ca 20,000 protein-coding genes. To date, over 5,000 KO mouse lines have been established, phenotyped and banked. KO mice are made freely available to international academic researchers.

The MRC became a founding partner of IMPC when it was established in 2011 and has recently committed to co-funding until the end of 2018 through its investments in MRC Harwell (principally the MLC). This reflects the MRC’s recognition of (i) the research community’s need for well-validated, comprehensively-phenotyped mouse KO lines and (ii) the need to uphold the principles of the “3Rs” through minimising the number of researchers independently creating the same knockout line.

Expectations of the pump-priming awards

The aim of this initiative is to capitalise on MRC’s (and others’) investments in the IMPC and make best use of the resources, data and tools available. We expect to provide small, flexible awards that allow take-up and use of the existing phenotyped and banked KO lines and resources. It is expected that this will catalyse more ambitious studies in the future.

Successful applicants will be expected to:

  • demonstrate research excellence and a proven track record in the proposed field of study. Applicants must have the necessary expertise and facilities to fully deliver their pump-priming objectives and take the work forward into larger, more detailed follow-on studies. Applicants must provide a clear picture of their research strengths and the innovative questions and research hypotheses that they plan to explore using the KO line(s).
  • have the necessary Home Office approvals and trained staff in place for the animal studies when, or soon after, the award is made

This call is aimed at existing and new users of MLC services and IMPC resources. Awards can involve collaborations with other academic groups and with industry.

Successful applicants will be expected to start their grants shortly after notification of the award and to finish on time. Funding supplements and extensions will not be available.

Intellectual property

Issues of intellectual property are outlined within the Material Transfer Agreement (MTA) to be signed by the PI, their host institution and the MLC (or other IMPC-provider of lines generated as part of the IMPC). The MTA must be completed before funds can be released. 

We expect MTAs to be signed off by January 2018: timely acceptance of the supplier MTA is a condition of this award and no negotiation of its terms may be entered into. As set out in the MTA, the provider of the knockout mouse line will not claim ownership of or any rights to any data, results, materials (including modifications) or intellectual property produced by the recipient scientists as a result of their use of the materials supplied.

An exemplar MTA is provided for illustrative purposes here: IMPC MTA‚Äč

Financial support available

Funding will support small, focused awards to provide support for distributing the lines to the receiving institution, establishing breeding colonies and undertaking early biological investigations. The primary purpose is to reveal biological insights that could prime larger, more ambitious work that would be supported through conventional funding routes.

Given the tightly focused nature of this initiative, funding will support direct research costs at 100% FEC as an Exception but will not support indirect or estates costs associated with FEC through standard TRAC methodology. Funding will only support staff employed to carry out the proposed laboratory research: PI/co-I salaries may not be requested where they do not carry out this work. Applicants should follow carefully the Award-specific ‘Step-by-Step JeS Guidance’ to ensure correct costs are submitted in their online application.

The funds may otherwise be used flexibly and, if appropriate, a proportion can be directed to the MLC to undertake some of the work proposed (e.g. specialist phenotyping assays or breeding programmes).

Funds can support:

  • shipping costs*
  • animal husbandry
  • consumables
  • technician/researcher time 
  • limited travel where partnerships are involved (e.g. with other academics, industry or MLC)

*Colonies may be established through receipt of frozen sperm or embryos (preferred), or as live breeding pairs (see FAQ for costs estimates). Preference for sperm/embryo shipment reflects the requirement of many host institutions to re-derive lines, and the fact that live mice shipped from overseas may require a quarantine period with associated welfare and cost implications. IMPC mouse repositories are distributed across the international partners: many lines will need to be shipped in, via the MLC, from overseas. Where live mice are sought, researchers should provide a clear justification in their proposal, explaining why frozen sperm/embryos are not suitable.

Applicants can request a single KO line or a small number of lines. Where more than one knockout line is requested, the scientific case for support will need to clearly justify the scientific value of the integrative approach. Regardless of the number of lines to be explored, application costs must not exceed £20-40k.

Additional limitations to financial support available:

  • capital funds for new equipment are not available through this call.
  • while the award may involve skills development as part of training activities, funding cannot be used to establish, part-fund or financially sustain PhD studentships. If PhD students will carry out work on the Award, a cover letter should describe how the planned work complements and builds on their PhD scientific objectives and development goals.
  • costs related to obtaining animals licences, publication costs or travel to conferences are not eligible. However, some travel to meetings with relevant collaborators may be requested. 

Eligibility

The research activities proposed must fall within the remit of the MRC. This call follows standard MRC and RCUK eligibility criteria* and is open to UK-based researchers who can show they will direct the proposed research and be actively engaged in carrying it through. Eligible institutions include UK higher education institutions and all Independent Research Organisations (IROs) listed on the RCUK web page.

*We do not expect MRC’s large and flexible strategic investments (e.g. institutes, units, regenerative medicine hubs etc) to need to access these small funding packages, given existing substantial, long-term funding that can be deployed to support this type of work. 

*Where a research group has substantial funding for research in areas highly similar to the application, the Award Panel will consider whether this could reasonably be expected to deliver the plan of work outlined. Applications that seek to conduct research which clearly has no other funding route will be prioritised for funding. Applicants are asked to list all current grants held in their CVs and can provide clarification about the distinctiveness of these in a Cover Letter. We strongly advise applicants to discuss any ambiguities around funding with the Programme Manager before submission via Lindsay.Wilson@headoffice.mrc.ac.uk

Commercial and industrial organisations are not eligible as lead investigators/institutions, but are able to participate through a sub-contract or partnering relationship with an institution eligible for direct receipt of funds. If an industrial collaboration is proposed, then applicants should submit a MICA form as part of their application.

There is no limit to the number of applications per higher education institution (HEI) or research institution. 

How to apply

The submission process will be single stage and applicants should follow the steps below:

Step 1: Check availability of the knockout of interest by searching the IMPC database. If the knockout is not yet available or is only available as a non-phenotyped, ES cell line, it cannot be sought through this call. 

Step 2: Email the Mary Lyon Centre at impc@har.mrc.ac.uk to outline the mice you require: they will confirm availability and provide a quote for shipping costs to you which should be incorporated into your application costs.

Step 3: It is essential that applicants carefully read this call’s Frequently Asked Questions and follow this Award’s Step-by-Step JeS Application Guide when applying.

Clear justification of animal use is paramount, including:

  • justification for the use of the mouse model over in vitro approaches or other animal models
  • whether existing data suggests the phenotype will exacerbate severity of procedure, and if so, how this might be mitigated 
  • demonstrated excellence in experimental design, as set out in Award specific Step-by-Step JeS Application Guidance, including justification of numbers, effect size, power calculations and avoidance of bias


The above will be key considerations for the Award Panel. Failure to provide this information in your application will lead to its rejection, and there will be no opportunity to supply additional information after the application has been submitted.

Step 4: Establish if any collaborations or outsourcing are required, and agree associated costs. Discuss any MLC outsourcing requirements via impc@har.mrc.ac.uk. If a substantial proportion of outsourcing work is to be undertaken by MLC or another body, applicants should discuss their plans with the MRC before formal submission by e-mailing lindsay.wilson@headoffice.mrc.ac.uk.

Step 5: Complete the application process on JeS. As this award differs from standard awards in its requirements, a step-by-step guide to the JeS application process is provided. Notable differences include:

  • the Case for Support is shorter than in standard applications. It must be no longer than 4 pages, including references. An additional 1 page Methodology and Experimental Design Annex must be appended to it, taking the total number of permitted pages to 5.
  • there are restrictions around what the award will fund, most notably in relation to indirect costs, PI /co-I salary and PhD students.
  • clarification of other awards held and the role, if any, of PhD students may need to be provided in a cover letter.

The following attachments are permitted: 

  • Cover letter e.g. if PhD student involvement needs to be explained (see Financial support available) or eligibility for Award funding needs to be explained (see Eligibility). 
  • Case for Support (4 pages, with a 1 page Annex)
  • CVs and separate List of Publications of named Investigators, including details of all current funding (PI & Co-I) (maximum 2 pages per CV plus 1 page for key publications. Guidance on CV format is provided on our guidance for applicants page).
  • Letters of support (only compulsory from Project Partners if present: further guidance can be found on our guidance for applicants page)
  • MICA and Heads of Terms forms should be appended if the study involves collaboration with industry
  • The following should not be attached: (i) Justification of Resources, (ii) Pathways to Impact, (iii) Data Management Plan, (iv) Additional Costs Proforma: NHS Support and Treatment Costs, (v) Technical Assessment, (vi) Final/Interim Report, (vii) Gantt Chart/Work Plan
You must submit your application to MRC by 4pm (16:00 BST) on Thursday, 6 July 2017.

Assessment criteria

Applications will be assessed, and funding decisions reached, by a specially-convened group of experts taken from across the MRC’s Research Boards. Additional referee comments will not be sought. Applicants will not have the opportunity to respond to any issues raised by the Group.

Applications will be evaluated against the following criteria, noting that the focus of individual proposals may vary depending on the experimental work proposed and the available research environment:

  • does the proposal meet the aims and expectations of the call?
  • does the proposed research show sufficient academic merit in quality and novelty?
  • does the proposed research have potential to underpin future grant applications? 
  • is there appropriate justification for the use of the mouse model and demonstrated excellence in experimental design (as explained in the Award’s specific ‘Step-by-Step JeS Application Guidance’), including severity of procedures, justification of numbers, effect size, power calculations and avoidance of bias?
  • is the study as a whole well-designed, with appropriate methodology and appropriate data analysis tools?
  • does the team have the necessary expertise and experience to carry out the proposed study?
  • where relevant, is it clear that the research should not be expected to be supported via existing awards held by the applicants?
  • are all the necessary requirements to carry out the study in place or available, and will they continue to be available if the award leads to future funding?
  • are all appropriate animal licences in place, or do they have the potential to be in place soon after the award has been made?
  • will the activities be appropriately managed?
  • is the project feasible and does it offer value for money?
  • have any ethical issues been adequately identified and addressed?

Applicants should check their completed Application Forms against the assessment criteria above prior to submission to make sure that they have addressed all points. 

Please note that only high level feedback will be provided to applicants following the Group’s decisions.