Full Text CA-97-011 NOVEL TECHNOLOGIES FOR EVALUATION OF MOLECULAR ALTERATIONS IN TISSUE NIH GUIDE, Volume 26, Number 2, January 17, 1997 RFA: CA-97-011 P.T. 34 Keywords: Biology, Cellular Biology, Molecular Gene Products Genetic Manipulation National Cancer Institute National Institute on Deafness and Other Communication Disorders Letter of Intent Receipt Date: February 15, 1997 and August 15, 1997 Application Receipt Date: May 8, 1997 and November 13, 1997 PURPOSE The Technology Development Branch of the Cancer Diagnosis Program, Division of Cancer Treatment, Diagnosis and Centers (DCTDC), National Cancer Institute (NCI) and the Division of Human Communication of the National Institute on Deafness and Other Communication Disorders (NICDC) invites applications proposing the development of novel technologies to facilitate generation of a comprehensive molecular profile of human tissues. Development of these innovative technologies is intended to impact the discovery process in research on the biology of human disease at the level of both gene discovery and molecular cellular biology. This initiative supports development of efficient, cost effective, sensitive technologies to permit the simultaneous, rapid evaluation of the spectrum of molecular alterations in tissue specimens and, ultimately, in single cells. These technologies can be designed to detect genome-wide molecular alterations at the level of DNA, RNA or protein. Investigators may propose technologies to scan the entire genome of a cell or tissue for constellations of cytogenetic changes or other DNA alterations. They may also propose development of technologies to identify changes in gene expression at the level of both RNA and protein. Technologies to evaluate the function status of proteins including proteins of cellular regulatory pathways are also appropriate. As a secondary goal, this initiative is intended to encourage the development of all components of integrated analytical systems including preparation of samples, sample analysis and appropriate informatics systems for data collection and analysis. Applications may be submitted as either research project grants (R01s) or exploratory/developmental grants (R21s). Investigators with sufficient preliminary data are encouraged to apply for funding using the R01 grant mechanism. Use of the R21 mechanism is designed to support applications where insufficient preliminary data has been generated to support a full R01 application. Approximately $1.5 million from NCI and $150,000 from NIDCD will be available for each receipt date. It is anticipated that six to eight applications will be funded following each round of review. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Novel Technologies for Evaluation of Molecular Alterations in Tissue, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit, and nonprofit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications may be from single institutions but collaborative studies between companies developing technologies and institutions with clinical resources and expertise are also encouraged. Racial/ethnic minority individuals, women and persons with disabilities are encouraged to apply as principal investigators. MECHANISM OF SUPPORT Support for this program will be through the National Institutes of Health (NIH) research project grant (R01) and exploratory/developmental grant (R21) mechanisms. The R21 mechanism is designed to support applications proposing novel technologies where insufficient preliminary data has been generated to support a full R01 application. The total budget for R21 applications should not exceed $100,000 and the project period should not exceed three years. R21 grants are not renewable but the project can be recompeted through other mechanisms such as R01 grants. Proposals not meeting the R21 criteria should propose use of the R01 grant mechanism. The total project period for the R01 applications should not exceed four years. Applicants will be responsible for the planning, direction and execution of the proposed research project. The anticipated award dates are September 30, 1997 (1st application receipt date) and July 1, 1998 (2nd application receipt date). Awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement. FUNDS AVAILABLE Approximately $1.5 million from NCI and $150,000 from NIDCD will be available for each receipt date. It is anticipated that six to eight applications will be funded following each round of review. The number and size of awards may vary depending on the number of meritorious R01 and R21 applications received. Grant awards will be contingent on the receipt of high quality applications and the availability of funds. RESEARCH OBJECTIVES Background Recent advances in our understanding of the complexity of the molecular alterations underlying human disease processes and continued progress toward obtaining the complete sequence the human genome have provided an opportunity to change the way research in human disease is carried out. The continued development of new and/or improved technologies for the simultaneous evaluation of large numbers of molecular alterations in tissue specimens will build on these advancements and will develop the contextual information necessary to fully understand molecular processes underlying human disease. This initiative will support the development of technologies to evaluate all or a subset of molecular alterations in human tissue specimens and, ultimately, in single cells. These technologies will facilitate the evaluation of the relative contribution of specific molecular alterations to disease processes. The NCI has established the Cancer Genome Anatomy Project (CGAP) in order to capitalize on the exciting advancements in cancer molecular biology and genetics and the genome initiative. CGAP has two initial goals: developing an index for all genes expressed in tumor tissue and developing novel technologies for the analysis of the molecular phenotype of tumor tissue or cells. This initiative addresses the second goal of CGAP by supporting the early stages of technology development. These technologies are intended to facilitate development of molecular profiles of tumor cells. These molecular profiles will identify new targets for research and will facilitate the generation of new testable hypotheses. These technologies will impact the discovery process in cancer biology research at the level of both gene discovery and molecular cellular biology. Once developed, these technologies will provide information about the molecular mechanisms underlying tumor initiation and progression. This information may ultimately be useful clinically by facilitating more effective cancer detection, improved diagnosis and prognosis, selection of more effective therapies for individual patients and more accurate monitoring response to therapies. Research Goals and Scope This RFA is intended to encourage applications from investigators proposing the development of technologies for the evaluation of molecular alterations in tissues. The novel technologies developed in response to this initiative will impact gene discovery and molecular cellular biology research, but should ultimately be appropriate for automation and adaptation to high-throughput applications. To be useful, the technologies should be sensitive, specific, efficient and cost effective. Investigators may propose the development of technologies to analyze the molecular profile of tissue at all levels of cellular function. For example, at the nucleic acid level, technologies may be proposed for identification of genetic alterations genome wide. These may include cytogenetic alterations or spectra of point mutations such as all possible mutations in a single gene or mutations in multiple genes, including genes that are members of cellular regulation pathways. Technologies to evaluate deletions, amplifications and other DNA alterations also will be considered responsive to this RFA. Technologies to determine patterns of gene expression, including changes in patterns of DNA methylation, are also appropriate. Protein-based technologies are currently at an early stage of development and are particularly encouraged. Applications for technologies to effectively determine patterns of protein expression and the status of proteins functioning in pathways of cellular regulation are responsive. Technologies to identify patterns of protein/protein or protein/nucleic acid interactions or post-translational modifications of proteins that result in changes in protein function are also appropriate. Investigators responding to this RFA should focus their proposal on the development of molecular detection technologies. Discussion of other aspects of an integrated analytical system may be presented and may be proposed as part of the supported research, however. The detection technologies developed under this initiative will require associated technologies in order to maximize their utility. An effective method of preparing appropriate sample materials from tissue will be necessary, for example. Information systems for the acquisition, analysis and management of research data will also be required. Development of these technologies may require an interdisciplinary team approach to research. Collaborations among clinical and academic investigators, basic researchers developing the technologies, engineers and specialists in bioinformatics are encouraged. The applications should propose development of appropriate technologies and studies to demonstrate their utility in analysis of tissue specimens. The emphasis of this initiative is the application of the technologies to the analysis of human disease but use of other mammalian systems may be proposed for early stage technology development and proof of principle studies. 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 new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. 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 reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by February 15, 1997 (1st application receipt date) or August 15, 1997 (2nd application receipt date), a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: James W. Jacobson, Ph.D. Division of Cancer Treatment, Diagnosis and Centers National Cancer Institute 6130 Executive Boulevard, Room 513, MSC 7388 Bethesda, MD 20892-7388 Telephone: (301) 496-1591 FAX: (301) 402-1037 Email: JJ37D@NIH.GOV APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grant. These forms are available at most institutional offices of sponsored research; 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@odrockm1.od.nih.gov, and from the NIH program administrator listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it might not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. Submit a signed, type-written original of the application, including the Checklist, and three signed photocopies in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, SUITE 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) To expedite the review process, at the time of submission, send two additional copies of the application to: MS. TOBY FRIEDBERG REFERRAL OFFICER NATIONAL CANCER INSTITUTE EXECUTIVE PLAZA NORTH, ROOM 636A 6130 EXECUTIVE BOULEVARD, MSC 7405 BETHESDA, MD 20892-7405 ROCKVILLE, MD 20852 (for express/courier service) Telephone: (301) 496-3428 FAX: (301) 402=0275 Applications must be received by May 8, 1997 (1st application receipt date) and November 13, 1997 (2nd application receipt date). If an application is not received by these dates, it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantially revised application, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and for responsiveness by the NCI program staff, in consultation with the NIDCD program staff. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, DRG staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI in accordance with the review criteria stated below. As part of the initial merit review, a process may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and will be assigned a priority score. All applicants will receive a summary statement consisting of the reviewers' written comments. Summary statements for competitive applications will also contain a summary of the review committee's discussion. The second level of review will be provided by the National Cancer Advisory Board. Review criteria that will be used to assess the scientific merit of an application are: o scientific and technical merit and novelty of the proposed technologies; o appropriateness and adequacy of the experimental approach proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; NOTE: Although R21 applications must meet all of the above criteria, they are not required to have extensive preliminary data in support of the proposed research project. The initial review group will also examine the provisions for the protection of human and animal subjects, the safety of the research environment, and conformance with the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. AWARD CRITERIA The following criteria will be considered in making funding decisions: the quality of the proposed project as determined by peer review; the responsiveness of the proposed project to the goals of this RFA; and the availability of funds. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: James W. Jacobson, Ph.D. Division of Cancer Treatment, Diagnosis and Centers National Cancer Institute 6130 Executive Boulevard, Room 513, MSC 7388 Bethesda, MD 20892-7388 Telephone: (301) 496-0591 FAX: (301) 402-1037 Email: JJ37D@NIH.GOV Kenneth A. Gruber, Ph.D. Division of Human Communication National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, Room 400-C, MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 402-3458 FAX: (301) 402-6251 Email: kenneth_gruber@nih.gov Direct inquiries regarding fiscal matters to: Ms. Dawn Hewitt Grants Administration Branch National Cancer Institute 6120 Executive Boulevard, Room 243, MSC 7150 Bethesda, MD 20892-7150 Telephone: (301) 496-7800, ext. 202 FAX: (301) 496-8601 Email: HEWITTD@GAB.NCI.NIH.GOV Ms. Sharon Hunt Grants Management Branch Division of Extramural Activities National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, Room 400-B, MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 402-0909 FAX: (301) 402-1758 Email: sh79f@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.394, Cancer Detection and Diagnostic Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74 and Part 92. 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 recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. .
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