SECOND INITIATIVE IN SYSTEMS BIOLOGY

SB 24/2006 SUBJECT: SECOND INITIATIVE IN SYSTEMS BIOLOGY MEETING: 13 JUNE 2006 SUMMARY This paper sets out the proposed terms of the second BBSRC/EPSRC initiative in Systems Biology and requests approval of these terms from BBSRC Strategy Board. ACTION The Board is invited to DISCUSS and APPROVE the call for proposals to be issued in September 2006. Science and Technology Group June 2006

BACKGROUND 1. BBSRC launched its first research initiative in Systems Biology during 2004 through its Integrative and Systems Biology (ISB) Strategy Panel. After screening a number of outline proposals in the first call, and inviting full proposals, three centres were funded at the universities of Manchester and Newcastle Upon Tyne and Imperial College, using resources provided by both BBSRC and EPSRC. A second call for proposals was launched in 2005 and following a similar review process, three further centres were funded at the universities of Nottingham, Edinburgh and Oxford. The total commitment to the Centres for Integrative and Systems Biology is 46.3M over five years including 7.8M from EPSRC. 2. Funding provided by BBSRC and EPSRC for the six centres comprised support for key staff posts, equipment and running costs representing a contribution to the infrastructure to generate the critical mass of capability to undertake systems level research. In addition, each centre was provided with limited funds for undertaking research projects in systems biology. RECOMMENDATIONS FOR THE SECOND INITIATIVE IN SYSTEMS BIOLOGY 3. The ISB Panel recommended that there should be a second initiative in systems biology. The call for proposals should be directed towards supporting a range of research projects in systems biology across the entire remit of BBSRC. These projects should be for a period of up to five years duration and support multiple staff posts to ensure there was the capability of undertaking both modelling and experimental approaches, so maintaining the multidisciplinary skills necessary for systems level studies. Due to the likely complexity of the proposals, an outline (or Expression of Interest; EOI) stage was strongly recommended. The research committees were consulted on the second initiative and all of them recommended that the second initiative should be implemented by the ISB Panel. A further 25M of BBSRC funding is available for commitment to projects received under this initiative. 4. A draft of the call for proposals for systems biology for the second initiative is attached at Annex 1. This call has been drafted by the Office based on: the advice and recommendations of the ISB Panel; discussion in the Office, based on lessons learned from the implementation of the Centres for Integrative Systems Biology initiative, and implementation of other large-scale initiatives in BBSRC.

CO-SPONSORSHIP 5. EPSRC has expressed an interest in co-sponsoring this initiative and is expected to contribute additional funds to the call. These funds would be given to facilitate the building of multidisciplinary teams through the engagement of physical scientists, engineers and mathematicians. 6. The Office is currently engaged in discussion with MRC over the co-sponsorship of applications where these are of potential interest to MRC, e.g., in physiological systems modelling. Training 7. BBSRC has traditionally used separate mechanisms to support postgraduate training programmes associated with initiatives. Although the draft call for proposals clearly states that postgraduate training programmes are not available through the call, the Office is currently investigating possible mechanisms that will permit simultaneous assessment of research and training requirements through both the EOI and the full proposal stage. Involvement of the Studentships and Fellowships Strategy Panel will be sought in the assessment of these proposals. TIMESCALE FOR THE COMMITMENT OF FUNDS 8. It is anticipated that with a launch date of September 2006 for the Expressions of Interest stage, full applications would be assessed in early Autumn 2007. If this timescale is followed, the first funds would be committed to projects in November or December 2007. If insufficient high-quality applications are submitted to the call, the Office will schedule a second call to be implemented thereafter. FEATURES OF THE SECOND INITIATIVE Data Sharing Policy 9. BBSRC intends to align this initiative with the principles set out in the BBSRC data sharing policy. The initiative represents a good model system to test the data sharing policy because systems biology is an area that will clearly benefit from wider data sharing activities. Therefore, applicants will be expected to explain how they plan to make data arising from these projects available to a wide range of users to comply with the Policy. Full applications will be assessed against criteria based upon the Policy; EOIs will therefore need to demonstrate that applicants have given due consideration to: the formal mechanisms for sharing of data within the project; the formal mechanisms for sharing data with the wider community; the resources required to fulfill these requirements.

10. The Call for Proposals will be modified in the light of the Strategy Board discussion on the BBSRC Data Sharing Policy. Value of grant proposals 11. The Office has suggested that instead of the ISB Panel s recommendation of funding in the range 1-3M over five years, funding of 2-4M would be more appropriate. With the introduction of full economic costing, the size of a grant employing a single research assistant for three years has risen to c. 350K. Thus employing two research assistants for five years will cost in excess of 1M. Recommending an upper level of 4M over five years provides the opportunity to employ up to six research assistants on a project. Allowing applicants to apply for between three and six staff posts per project should provide a more realistic range of staffing resources. Development of tools and technologies 12. BBSRC funding for this initiative includes an element for e-science in support of Systems Biology. The initiative therefore invites applications which address the development of electronic tools in support of systems biology research, to ensure integration of e-science with Systems Biology. Involvement of industry 13. The call for proposals requires the applications to be associated with named companies. This should help to ensure high strategic relevance, contribute to BBSRC s responsibilities under the cross-government Technology Strategy, and the council s own Technology Strategy, in which Exploiting Systems Biology is a priority. CONSULTATION 14. The draft call for proposals presented has been approved by the members of the ISB Panel. Comments have also been received from members of the Tools and Resources Strategy Panel. ACTION 15. The Board is invited to DISCUSS and APPROVE the call for proposals to be issued in September 2006.

ANNEX 1 CALL FOR EXPRESSIONS OF INTEREST: SYSTEMS APPROACHES TO BIOLOGICAL RESEARCH INTRODUCTION Following the Centres for Integrative Systems Biology (CISB) initiative, the BBSRC and EPSRC announce a second joint initiative in Systems Biology. OBJECTIVES The aim of the Systems Approaches to Biological Research (SABR) initiative is to work in partnership with relevant UK universities and research institutes to establish a range of Systems Biology research projects. The objectives are to: support a range of high quality Systems Biology projects, thereby further establishing Systems Biology research in UK universities and research institutes; encourage cross-disciplinary interactions between the biosciences, physical sciences, mathematical/computational sciences and engineering; contribute to the generation of postdoctoral staff trained in Systems Biology research in the UK; contribute to improved interactions between the science base and industry. The initiative will be focused on the following: Systems approaches to studying strategically important problems across the range of BBSRC s remit, integrating experimental and predictive approaches. e-tools to support Systems Biology research. FUNDING RANGE Expressions of Interest are invited from researchers meeting BBSRC eligibility criteria (see Further Particulars) for proposals in the range of 2-4M, for up to five years duration. A budget of up to 25M is available from BBSRC, and additional funds are available from the EPSRC (see Further Particulars). REVIEW OF PROPOSALS This call will be implemented in two stages: a call for Expressions of Interest (EOIs), which is the current stage, and a full application stage. Applicants successful at the EOI stage will be invited to submit full proposals, at the second stage. All proposals will be reviewed and finally ranked by the BBSRC Integrative & Systems Biology Strategy Panel [hyperlink to ISBP homepage].

TIMINGS The deadline for submission of EOIs is [date] November 2006 (see Further Particulars). EOIs will be assessed in January 2007, with full applications to be submitted by May 2007. Full applications are likely to be assessed in September 2007. It is anticipated that grant announcements will be made by end of November 2007. Expressions of Interest should be submitted according to guidance provided in the Further Particulars by 4pm, [Date, 2006]. FURTHER PARTICULARS WHAT ARE THE KEY CHARACTERISTICS THAT CONSTITUTE INTEGRATIVE SYSTEMS BIOLOGY, WHICH MUST BE ADDRESSED IN ANY PROPOSAL UNDER THIS INITIATIVE? There are many different definitions of systems biology, and many possible approaches to the development of systems biology research, appropriate to different research challenges. The following list is indicative rather than prescriptive, but identifies the key characteristics of Integrative Systems Biology: The capability to undertake predictive biology: the ability to manipulate the experimental data, and to develop the theoretical base (modelling) to understand those data, to test ideas and to optimise the next hypotheses to be tested experimentally, with the final goal of understanding the system s properties (such as mechanisms of robustness of the biological system) from the mathematical model. An integrative approach to the subject area. This means research involving all known applicable components in the system being studied, and working across relevant levels of biological organisation. It also means studying the relationships and interactions between various parts of the biological system. This is normally linked to having a well-characterized biological model. Access to and ability to generate large experimental datasets. These will often be generated from high-throughput (HTP) technologies, and will be associated with the necessary data capture, handling and storage skills and facilities. A mix of inputs from the biological, physical, engineering, mathematical and computational sciences.

ESSENTIAL CRITERIA Proposals are encouraged from any field across the range of biological sciences within BBSRC s remit. This includes research on integrated complexes or networks of interacting molecules as well as studies on higher, multicellular levels of organisation. An example of the latter type is in modelling physiological systems such as the liver. If the proposed research is based upon a model organism, applicants are expected to have given due consideration to existing national or trans-national facilities for data sharing as part of their proposed approach. Applicants must set out an objective-led research project that describes either (i) the study of the biological model using a systems approach (as described above), demonstrating access to the requisite range of experimental and computational facilities, or (ii) the development of electronic tools that will support the development of systems biology research (see above), each supported by the necessary technical expertise. The Expression of Interest must involve staff with the relevant experience as part of the core of Principal and Co- Investigators. Ideally this should include proposals to develop new theory and modelling techniques. Applicants should demonstrate an awareness of the need for outreach and engagement to advance national capability in Systems Biology, including interactions with the BBSRC/EPSRC Centres for Integrative Systems Biology and international and industrial collaborations. Applicants should demonstrate interactions with named companies through their research projects. In order to further encourage engagement with industry, the Industrial Partnership Awards (IPAs) scheme will apply to proposals submitted under this initiative (see http://www.bbsrc.ac.uk/funding/research/grants_booklet.pdf, sections 2.11-2.18). In addition to the above, applicants should also give due consideration to the following. These guidelines draw upon experience gained from the CISB initiative. Joint applications between institutions will be considered; funding such proposals will be subject to clear strategies for ensuring the necessary integration. The lead applicant for the joint project must submit a cover letter summarising the nature of the joint proposal, and the scientific case for support must only be made in the lead application. Applicants are advised to contact BBSRC (see Contact details) to discuss any intention to submit a joint proposal. An appropriate time commitment (i.e. at least 3-5 hours per week) to the project by the proposed Principal Investigator and key Co-Investigators is advised in order to ensure appropriate management and multidisciplinary co-ordination.

New academic posts at the interface between biology and the physical/mathematical sciences are seen as key to retaining and developing Systems Biology capability within the academic research base. Funding for proleptic appointments the establishment of new Systems Biology research leaders (Lectureships/Chairs) with initial funding from the grant will be considered. Funds for postgraduate training programmes are not available through this call. Training in this area is acknowledged as being important for capacity building, and is being developed through other routes. e-tools TO SUPPORT SYSTEMS BIOLOGY RESEARCH The initiative is able to support the development of electronic tools and enabling technologies for Systems Biology research. Applicants should describe the electronic tools they wish to develop and how they will support Systems Biology research. Proposals will be greatly enhanced if they demonstrate interactions with current Systems Biology research to illustrate the utility of the tools being developed. This part of the call is complementary to the BBSRC's Technology Development Research Initiative [insert TDRI hyperlink] and reflects the research councils commitment to embed e-science in systems biology research. BBSRC is developing a data sharing policy and further details of the project can be found at [DSP website hyperlink]. Applications to this call should consider the practical requirements for data sharing (both within consortia and with the wider community) and request appropriate resources on their applications. Proposals seeking to develop a data sharing infrastructure for Systems Biology would also be welcome. HOW TO APPLY: FORMAT OF EXPRESSIONS OF INTEREST Applicants should initially submit an Expression of Interest (EOI) of up to four sides of A4 text (font size: 12 point, Times New Roman) to include: 1. Names of all applicants (the PI, co-investigators and collaborators) 2. Description of the project (the science case) 3. Management of the project (s) 4. Resources required from the research councils (please describe any financial contributions to be made to the project through industrial or other forms of collaboration including any institutional contribution) 5. Current relevant external funding CVs of all applicants (maximum of 2 pages per applicant) should be appended to the EOI. Applicants successful at the EOI stage will be invited to submit full proposals, at the second stage. All proposals will be reviewed and finally ranked by the BBSRC Integrative & Systems Biology Strategy Panel [hyperlink to ISBP homepage].

SUBMISSION Expressions of Interest should be submitted according to guidance provided in the Further Particulars by 4pm, [Date, 2006], to the following email address: [named.mailbox@bbsrc.ac.uk] ELIGIBILITY Normal BBSRC rules on eligibility apply (see http://www.bbsrc.ac.uk/funding/research/grants_booklet.pdf). This initiative is open to all eligible UK universities, Academic Analogues, BBSRC and other eligible institutes. NATURE OF SUPPORT Grants will be made on a Full Economic Costs (FEC) basis: typically in the 2-4M funding range, of up to 5 years duration. Proposals may therefore request up to 4M from in total from BBSRC and EPSRC, of which some funds would be expected to be deployed specifically to facilitate the building of multidisciplinary teams and project management. Prospective applicants wishing to discuss the EPSRC funding component in this initiative are advised to contact [EPSRC contact] (see Contacts section) before submitting their outline to BBSRC. Further advice on Dual Support (FEC) arrangements is available at: http://www.pparc.ac.uk/jes/dualsupport.asp. INITIATIVE LAUNCH SEMINAR BBSRC and EPSRC will organize a town meeting of 2-3 hours duration, which will be announced in due course. Prospective applicants who may wish to attend this event should contact Dr Abbasi by e-mail, as below, to register their interest and be added to a mailing list for updates. FREQUENTLY ASKED QUESTIONS [Frequently Asked Questions Page.] CONTACTS General scientific enquiries should be addressed to: Dr Sophia Abbasi, Programme Manager, Systems Biology BBSRC Polaris House, North Star Avenue Swindon SN2 1UH Telephone: 01793 414 666 Email: sophia.abbasi@bbsrc.ac.uk

Scientific enquiries for the EPSRC component should be addressed to: [EPSRC Contact], Head of Life Science Interface EPSRC Polaris House, North Star Avenue Swindon SN2 1ET Telephone: 01793 41x xxx Email: [firstname.lastname@epsrc.ac.uk] Administrative enquiries should be addressed to: Miss Tracy Baillie, Administration Manager, CSU BBSRC Polaris House North Star Avenue Swindon SN2 1UH Telephone: 01794 413 225 Email: tracy.baillie@bbsrc.ac.uk