PA-98-024: SUPPLEMENTS FOR THE STUDY OF COMPLEX BIOLOGICAL SYSTEMS

Department of Health
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SUPPLEMENTS FOR THE STUDY OF COMPLEX BIOLOGICAL SYSTEMS Release Date: January 16, 1998 PA NUMBER: PA-98-024 P.T. National Institute of General Medical Sciences PURPOSE The purpose of this initiative is to support new quantitative approaches to the study of complex, fundamental biological processes by encouraging non-traditional collaborations across disciplinary lines. The National Institute of General Medical Sciences (NIGMS) will provide supplements to existing NIGMS grants to support the salary and expenses of collaborating investigators such as physicists, engineers, mathematicians, and other experts with quantitative skills relevant to the analysis of complex systems. It is expected that the collaboration will result in new directions for the parent project, or new research projects that will compete for independent funding. ELIGIBILITY REQUIREMENTS The principal investigator must have an active investigator- initiated research grant funded by NIGMS (R01, R37, or P01). In all cases, the parent grant must have at least one year of support remaining at the time of the supplemental award. An investigator will be allowed one supplemental award at a time under this program. Because the supplements are intended to develop cross- disciplinary research collaborations, the prospective collaboration must propose new approaches to the subject area of the parent grant. Therefore, the expertise of the prospective collaborator should not substantively overlap that of the principal investigator. The collaborator need not have prior experience with biological problems, but must have established credentials in the area of his/her expertise. The proposed research project also must be distinct from the collaborator’s ongoing research. Prospective collaborators with NIH support are not eligible for this program unless a compelling case is made that the existing NIH grant neither overlaps, nor is an alternative source of funds for, the proposed collaboration. Investigators are encouraged to contact the program director of the parent grant or NIGMS staff listed under INQUIRIES, to discuss eligibility requirements. Applications may be submitted by foreign, domestic, for-profit and non-profit organizations, both public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Principal Investigators are encouraged to consider collaborators who are in the racial/ethnic minority, women, and persons with disabilities. MECHANISM OF SUPPORT The intent of this initiative is to provide for an expansion of the scope of the parent grant. Therefore, awards will be made through the peer-reviewed competitive supplement mechanism. Salary, fringe benefits and travel expenses (if needed to establish the collaboration) will be provided for the collaborating investigator. Additional funds may be requested for supplies and well-justified items of equipment. The term of award can extend to the end of the funded period. RESEARCH OBJECTIVES Research in the basic biomedical sciences has provided dramatic advances in our knowledge of the fundamental mechanisms underlying life processes. These advances owe their success in large part to a paradigm that focuses attention on a limited number of model systems and develops and uses analytic methods of exquisite sensitivity and specificity, such as genetics and the tools of molecular biology. The strategy has been to identify individual cellular components, elucidate their structure, function and regulation, and confirm their role at the cellular, subcellular and molecular levels of organization. Recent technological advances in the genomic sciences, moreover, promise to extend our information base to all the gene products of the cell, with an ever-increasing rate of data accumulation and need for analysis. NIGMS anticipates that biomedical research will become increasingly focused on the understanding of biological functions at a higher order of complexity. If the goal is to predict the behavior of the cell, tissue or organism, especially when perturbed by disease states, it will be necessary to discover and represent the contributing factors and the dynamics and system rules that govern the collective behavior of these factors. Mathematical models and simulations, with reliance on computers to handle large quantities of data, are among the tools that are being developed to analyze and represent complex processes. Promising research areas include, but are not limited to: 1) the analyses of patterns of gene expression and signal transduction in embryogenesis, 2) the description of forces modulating the interaction of molecules in dynamic, complex assemblies such as the mitotic apparatus, 3) the analysis of the control circuitry regulating the flow of metabolites at both gene and enzymatic levels, 4) the analysis of tissue and organ-level homeostatic mechanisms, and 5) the development of methods to identify genes and environmental influences that contribute to complex traits. Different levels of organization most likely will require different treatments, understanding the dynamics of cell motility may require entirely different approaches from analyzing complex gene-environment interactions that underlie drug action, or understanding systemic host responses to trauma, burn, or other injury. Generically, these types of problems reflect the traditional interests of the quantitative disciplines such as mathematics, chemistry, physics, engineering, and computer science. Although individuals with skills in these disciplines have a history of contributing to the understanding of biological phenomena, such as the solution of macromolecular structure, there are relatively few who have applied this expertise to the study of biological problems at more complex levels of organization. NIGMS recognizes that biomedical scientists have begun to express interest in understanding experimental systems at a higher level of complexity. Because often there are formidable obstacles to the development of cross- disciplinary collaborations, NIGMS offers this initiative to encourage and facilitate the process. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103 43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508- 14513) and in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 5/95) and will be accepted at the standard application deadlines as indicated in the application kit. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: ASKNIH@od.nih.gov. The title and number of this program announcement must be typed in Section 2 on the face page of the application. Information regarding active or pending sources of project-specific support available to the principal investigator and collaborator is an important part of the review and award process and must be included in the Other Support section page of the PHS 398. The application must provide the curriculum vitae of the proposed collaborating investigator, including a detailed list of publications. The application must include a specific research project based on the aims of the parent grant, but which expands the scope to incorporate new conceptual and/or technical quantitative approaches that are the basis for the collaboration. The research project may become the basis for the collaborator to seek independent funding or to cooperate in a continuing effort with the sponsoring NIGMS grantee. The research proposal must make clear the unique opportunity afforded by the collaborating investigator’s expertise to the quantitative analysis of complex biological problems. A letter of commitment from the collaborator must be submitted as a supporting document with the application. The letter should be countersigned by an institutional official if the collaborator is at a different institution than the one submitting the parent grant application. The completed original application and five legible copies must be sent or delivered to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) REVIEW CONSIDERATIONS Applications will be reviewed for scientific and technical merit by an appropriate initial review group of the Center for Scientific Review. Following the initial scientific-technical review, the applications will receive a second-level review by the National Advisory General Medical Sciences Council. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written review, comments on the following aspects of the application will be made in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in the assignment of the overall score. 1. Significance. Does the proposed collaboration add substantial value to the problem under study in the parent grant? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? 2. Approach. Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the parent project? Does the applicant acknowledge potential problem areas and consider alternative tactics? 3. Innovation. Does the collaborative project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? 4. Investigator and Collaborator. Are the investigator and collaborator appropriately trained and well suited for the collaborative project? Is the work proposed appropriate to the experience level of the principal investigator, the collaborator, and other researchers on the project (if any)? 5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment in order to establish a useful collaboration? Is there evidence of institutional support? AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to NIGMS. The following will be considered in making funding decisions: The quality of the proposed collaborative project as determined by peer review, the availability of funds, the extent to which the proposed collaborative project will recruit investigators of appropriate expertise, who might otherwise not have the opportunity, to contribute to the quantitative study of complex biomedical problems. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to either the program director listed on your award statement, or: Dr. James C. Cassatt Division of Cell Biology and Biophysics National Institute of General Medical Sciences 45 Center Drive, MSC 6200 Bethesda, MD 20892-6200 Telephone: (301) 594-0828 FAX: (301) 480-2004 Email: czj@cu.nih.gov Dr. Judith H. Greenberg Division of Genetics and Developmental Biology National Institute of General Medical Sciences 45 Center Drive, MSC 6200 Bethesda, MD 20892-6200 Telephone: (301) 594-0943 FAX: (301) 480-2228 Email: greenbej@nigms.nih.gov Dr. Michael E. Rogers Division of Pharmacology, Physiology and Biological Chemistry National Institute of General Medical Sciences 45 Center Drive, MSC 6200 Bethesda, MD 20892-6200 Telephone: (301) 594-3827 FAX: (301) 480-2802 Email: rogersm@nigms.nih.gov Direct inquiries regarding fiscal matters to either the grants management specialist listed on your award statement, or: Ms. Carol Tippery Grants Management Office National Institute of General Medical Sciences 45 Center Drive, MSC 6200 Bethesda, MD 20892-6200 Telephone: (301) 594-5135 FAX: (301) 480-1969 Email: tipperyc@nigms.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Numbers 93.821, 93.859, and 93.862. Awards are made under authorization of the Public Health Service Act, as amended and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro- Children Act of 1994, prohibits smoking in certain facilities (or in some cases, and portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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