This call is now closed for applications and is available for reference purposes only.
The Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Science Research Council (EPSRC) and Medical Research Council (MRC) are establishing a £25M UK Regenerative Medicine Platform (UKRMP) to address the technical and scientific challenges associated with translating promising scientific discoveries in this area towards clinical impact.
At its core, the first stage of funding supports interdisciplinary and complementary Research Hubs that together will provide a world-leading programme to promote the development of regenerative therapies by addressing key translational gaps.
To complement the recently established Hubs, the RC sponsors are inviting proposals to establish a high quality, collaborative research grouping that can assemble the capability needed to address key immune challenges in translational regenerative medicine, focussed on harnessing immunomodulatory approaches.
This is a revised call from that advertised in September 2012, with a broader remit informed by an Immunology/Stem Cell Workshop held on the 5th July 2013. Applicants are strongly advised to consult the Workshop report when considering how to frame their proposal.
Regenerative medicine is an interdisciplinary approach spanning tissue engineering, developmental and stem cell biology, gene therapy, cellular therapeutics, biomaterials (scaffolds and matrices), nanoscience, bioengineering and chemical biology. It may involve:
- transplantation of stem cells, progenitors or tissue;
- stimulation of dormant repair processes;
- using cells as delivery vehicles for therapeutic agents;
- engineered cells / synthetic biology.
Regenerative medicine has already provided significant medical advances in areas such as skin regeneration for burns patients and diabetic ulcers and the treatment of anaemia, and has the potential to go much further with next-generation products offering treatments with long term benefits or cures. The underpinning science is progressing rapidly, yet there are a number of developmental challenges which need to be overcome if we are to successfully translate promising discoveries for the benefit of patients as well as the UK economy. These are elaborated upon in the Research Council/TSB Strategy for UK Regenerative Medicine, published in March 2012.
As a response to these translational requirements, and to ensure that research addressing regenerative medicine connects seamlessly from discovery science through to clinical and commercial application, BBSRC, EPSRC and MRC are together establishing a UK Regenerative Medicine Platform (UKRMP) with the goals of:
- establishing interdisciplinary research hubs with the critical mass and expertise to address key knowledge-gaps in the translation of stem cell and regenerative biology towards application;
- providing the novel tools, platform technologies and engineering solutions needed for therapeutic development;
- creating a world-leading and fully connected national programme to pull through excellent discovery science in support of the commercial development and clinical delivery of regenerative medicine products.
Three UKRMP Hubs have recently been established, with a recently awarded fourth Hub, focused on pluripotent stem cell characterization, differentiation and scale-up, to be functional by the end of 2013 (detail to be available on the UKRMP website, autumn 2013).
The purpose of this call, for which £2M is available, is for the establishment of a fifth and final Hub with an immunological focus.
2. Aim of Hub
To undertake a coordinated programme of activity that will identify and begin to establish broadly applicable approaches to immunomodulation in support of the development and clinical testing of regenerative strategies.
This call is inviting applications that draw in relevant expertise across the stem cell biology, immunology and transplantation fields to address the modulation of both the innate and adaptive immune responses to enhance the survival and efficacy of cell and biomaterial implants in regenerative medicine. Understanding and overcoming immune rejection of cell–based transplants is a critical barrier to the clinical delivery of allogeneic regenerative medicine therapies. While approaches to controlling rejection through immune suppression are widely researched in the pharmaceutical sector, alternative strategies such as inducing host immune tolerance or enabling transplanted cells/tissues to evade host immunity are relatively under-explored. In addition, co-opting the immune system might be used to enhance the regenerative and repair efficacy of cell-based transplants by aiding, for instance, remodeling processes.
It is anticipated that the Hub will establish a foundation on which a programme of activity can be initiated to increase understanding of how the innate and adaptive immune systems impact upon cell‑based therapies, so as to develop approaches for modulating these responses; for example
- through the manipulation of effector components such as the niche, macrophages, regulatory T cells or NK cells,
- and potentially through providing access to, or characterization of, existing humanized animal models (note, the establishment of new models is not envisaged through this funding);
In addition the Hub will investigate a range of potential applications, covering one or more of:
- inducing central tolerance, for example through the use of tolerogenic dendritic cells or mixed chimaerism; reducing the immunogenicity of stem or progenitor cells, perhaps through co-opting mechanisms of ‘immune privilege’
- enhancing cell-based therapy efficacy
- harnessing aspects of immune evasion, as for example utilized in other host-pathology (e.g. cancer, pathogens) interactions;
The Hub to be funded under this call is expected to build a connected network of key players who together can:
i) identify the tractable issues and establish a multi-faceted approach to begin to address them;
ii) establish an evidence base and develop new methods, approaches and tools that can underpin further research activity in this domain, whether through the developing UKRMP programme or other funding sources in the longer term;
iii) establish a recognized repository of expertise in support of the wider regenerative medicine community.
The Hub to be established is also expected to connect with the other UKRMP Hubs given that their agendas all have an interest in immunological considerations, with the interactions likely to evolve during the course of the programme.
Connection to bioindustry is also encouraged, whether at the time of submission of the bid or during the evolution of the Hub.
A budget of up to £2M will be available over 3 years to establish a single national research Hub in this area. It is anticipated that the successful development of an Immunomodulation Hub will lead to access to further RC funding in the future.
3. UKRMP Hub Remit and Criteria
It is expected that the remit of the Immunomodulation Hub will be in keeping with overarching remit and criteria of all other Hubs which is to;
- provide a UK centre of expertise/knowledge with the necessary critical mass to address key translational challenges and provide new tools, protocols and resources with broad applicability that can and should be utilised by other UK research groups in academia and industry.
- assemble appropriate interdisciplinary activity to provide a UK competency that will be able to attract further partnerships and investment, and provide outputs that have broad utility even if developed using specific systems/diseases as exemplars;
- be proactively managed by a director/management team that will be empowered by the host institution(s) to be responsive to need within its theme and which will report annually to the UKRMP Programme Board;
- evolve during the course of the award and reach out to groups that best enable the Hub to meet its goals (see Networking Support);
- preferentially involve multiple groups from more than one location / University / industrial setting that have a proven track record in delivering internationally competitive research either in the basic sciences related to the identified themes or translating aspects for drug development or clinical protocols.
However, it is recognized that for this theme the Hub, which will receive funding for 3 years, will be more developmental in nature, with an enhanced focus on assembling the complementary and interdisciplinary research excellence necessary to have impact in this area, and initiating novel approaches that will provide routes to more substantive activity in the longer term.
Hence the successful application will ultimately be one which:
- demonstrates the formation of novel interactions based upon research excellence;
- provides innovation in addressing the identified challenges within the context of a broad but integrated approach;
- effectively links basic and clinical research groups;
- incorporates relevant cross-disciplinary expertise spanning the remits of the three Research Council sponsors;
- builds on a strong portfolio of existing Research Council investment, and demonstrates significant added-value to this;
- demonstrates strong scientific leadership;
- proposes a milestone-based programme of activity spanning work-packages or clustered developmental projects;
- includes appropriate project management to underpin coordination and collaboration within the consortium;
- promotes outreach activities to connect to other UK groups that provide complementary skills and resources;
- specifies an approach towards early engagement with regulators and anticipated hurdles for regulatory compliance where relevant;
- includes strong plans to facilitate engagement with (bio)industry and end-users outside of the Hub.
4. Funding Available
- A budget of up to £2M will be available to establish a single national research Hub in this area.
- The awards for the Hub will be administered by the MRC on behalf of the partners and subject to MRC terms and conditions.
- The request for funding should include plans for outreach and networking (with a dedicated budget of £10k per annum) – see below.
- The award will be for 3 years in the first instance. It is expected that successful delivery of the Hub’s approved objectives will lead to access to further RC funding, which will need to be considered in the context of the institutional support available. In order to assess this potential, a longer-term sustainability plan with demonstrable commitment by the host HEI(s) to ongoing support of the Hub at the end of the initial 3 year funding term must be submitted as part of the UKRMP application;
5. Support Available
- The Director’s salary costs for the portion of their time dedicated to scientific and management leadership of the Hub;
- Modest start-up costs for new positions to develop capacity or key positions central to the Hub’s success;
- Funds for new research and translational activities, in particular to support new interactions across the Hub and including collaborations with industry, NHS, etc;
- Funds to enable the Hub to develop and function as a cohesive regional or UK research focus (e.g. funds for pilot studies, support posts, common resources/datasets etc);
- Funds to provide a support/advisory service to collaborate with researchers working outside the Hub;
- User and public engagement, coordination and collaboration costs to bring the research closer to application and patients.
6. Networking Support
A key aspect of establishing the UKRMP Hubs is to build critical mass and provide focus on creating greater translational impact. The Hub will be provided with resource for networking activity to address key needs relevant to the Hub’s theme. This mechanism will help build connectivity and coherence in delivering the broader goals of the UKRMP.
£30k (£10k/pa) within the Hub award will be dedicated to support networking activities that further the objectives of the Hub and help address end-user and stakeholder needs. Examples of such activities could include:
- Initiating collaborations with industry and other end-users;
- Building routes for linking with the Cell Therapy Catapult;
- Networking across the UKRMP Hubs;
- Linking with other strategic initiatives in the regenerative medicine area, both within the UK and overseas;
- Coordinating resources to share /exploit equipment and other facilities;
- Organising workshops relevant to the Hub’s theme (which shouldn’t replicate or replace existing meetings organised by other stakeholders in the field.
This is not an exhaustive list, and bids to establish this UKRMP Hub will need to make the case for the resources they are requesting for networking activities, identified in detail for the first year of the award. All networking activities must identify the key deliverables and associated dissemination activities. The programme of activity will be reported to the UKRMP Programme Board on an annual basis, while networking activities beyond the first 12 months of the Hub award will also need to be approved by the UKRMP Programme Board.
Based on the advice of the UKRMP Programme Board and Executive Group, other UKRMP networking activities could be initiated if there is a gap or a specific intervention is needed. Ultimately the intention is to establish a coherent UK-wide networking structure that addresses the key needs of the community as identified through the ‘Strategy for UK Regenerative Medicine’.
7. Support Not Available
Funds cannot be requested for capital and refurbishment costs or infrastructure and core administrative services (secretarial, finance, personnel, computing support, estates and building maintenance) covered by the indirect cost component of FEC.
Funds cannot be requested for training awards, including studentships and fellowships.
Funds cannot be requested to support clinical trial activity. Due to the complex nature of such applications, it is more appropriate for these to be submitted separately to other appropriate response-mode schemes offered by the funders.
For administrative purposes, the UKRMP application will be led by a single UK academic institution or independent research organisation approved by the Research Councils. Applications from throughout the UK are eligible.
The Director must be the principal investigator on the proposal and be given appropriate status within the lead host institution to facilitate management and development of the Hub’s activities. The Director should be in a position to influence research programmes associated with the Hub, and must have full control over use of Hub funds.
Co-applicants are expected to be the leading scientists involved in delivering the Hub’s aims and objectives.
Partnerships with industry are encouraged. Applicants considering establishing collaboration with an industrial partner(s), are advised to refer to the guidance on MRC Industry Collaboration Awards (MICAs).
9. Application and Assessment Criteria
ALL applicants are required to discuss their proposals with Dr David Pan, UKRMP Science Manager, before submission. A brief abstract should be e-mailed in advance of discussions.
The purpose of the abstract is for administrative purposes only. This will allow the office to ensure that proposals are aligned with the remit of the call. No feedback will be given other than confirmation that the proposed bid is within scope and can be submitted. Abstracts should be top level and provide the underlying objectives and identify lead and key partners. It is recognized that final proposals are likely to continue to evolve right up to the application deadline, so they need not be restricted to the precise description provided within the abstract, although the full proposal must fully reflect its core elements. Abstracts must be submitted by 4pm Tuesday 1st of October.
Applicants will submit proposals through the RCUK Je-S system and be led by academic institutions. The deadline for full applications will be 4pm 31st October 2013.
Specific instructions for completing the case for support are detailed in the Guidance Notes for UK Regenerative Medicine Platform. Proposals will be externally peer reviewed before being considered by an expert review panel in February 2014. Final funding decisions will be made by the contributing funding partners represented through the UKRMP Executive Group. Awards will be announced in March 2014.
Proposals should describe:
- the critical and generic translational challenges to be tackled by the Hub;
- the gaps in knowledge, and how the Hub will address these and contribute to the development of therapies in the longer term;
- how what is being proposed is transformative and different from “business as usual;
- the level of innovation to be delivered through the programme of activity;
- the PIs / groups and, potentially, industrial partners involved as the core group;
- any additional skill sets that will need to be incorporated during the course of the programme;
- end-user groups that need to be engaged; for example, linkage with clinical teams, commercial partners and the TSB Cell Therapy Catapult. Consideration should also be given to complementarity and linkage with other relevant national and international strategic initiatives;
- how the collaborative approach will be developed and managed; a clear governance structure and project management plan is required;
- a plan for longer-term sustainability beyond the 3-year award;
- deliverables and potential milestones of progress; note that applicants will be asked to identify up to 3 key milestones (out of the expected broader set identified in the case for support) which will be described in more detail in a Milestone Form which is a required attachment to the proposal for this call.
The assessment will take account of the scientific opportunities and national capabilities presented. Consideration will be given to the:
– significance of the challenges to be addressed;
– novelty, importance and timeliness of the research;
– ability of the investigators to deliver the research proposed;
– strength and clarity of collaborations and end-user engagement;
– quality of the project management structure proposed;
– quality and suitability of the research environment and of the facilities;
– value for money;
– ethical considerations and governance arrangements.
Applicants are directed to the supplementary terms and conditions for RC grants introduced in the context of stem cell research, see for example Medical Research Council – MRC Terms and Conditions, section AC24. Hubs will be required to annually submit reports to MRC’s Electronic Valuation System (Researchfish; previously MRC e-Val).
Further details are available from Dr David Pan.
10. Contacts and Guidance
- Dr David Pan
Science Manager, UKRMP (on behalf of the BBSRC, EPSRC & MRC)
Telephone: 01793 416430
Guidance can also be sought from:
- Dr Nicola Goldberg (EPSRC)
Telephone: 01793 44447
- Dr Jef Grainger (BBSRC)
- Dr Jonathan Pearce (MRC)
Telephone: 020 7395 2271
11. Deadline Dates
Call Launch – 30th July 2013
Call open on JeS – 23rd August 2013
Submission Deadline for Abstracts – 4.00pm 1st October 2013
Submission Deadline for Full Applications – 4.00pm 31st October 2013
Funding Decisions – February 2014
Award Start Dates – 1st March through to 30th September 2014