$$XID RFA HG9201 HG-92-01 P1O1 ***************************************** NEW DNA SEQUENCING TECHNOLOGY IN SUPPORT OF THE HUMAN GENOME PROGRAM RFA: HG-92-01 P.T. 34; K.W. 1215018, 1002058, 0755045, 1004017 National Center For Human Genome Research Letter of Intent Receipt Date: January 31, 1992 Application Receipt Date: March 17, 1992 The National Center for Human Genome Research (NCHGR) invites applications for research projects to develop new approaches to DNA sequencing that will be rapid and cost-effective when applied to large-scale sequence analysis. INTRODUCTION The NCHGR sponsors basic and applied research concerned with the development and application of new technologies for the characterization and analysis of the human genome and the genomes of selected model organisms. The activities encompassed by the NCHGR program include genetic and physical mapping, DNA sequencing, informatics related to mapping and sequencing, and technology development that will facilitate all of these efforts. The NCHGR, in conjunction with the Department of Energy, recently formulated a five-year plan that identifies areas where further research, including technology development, is needed if the characterization of the human and other genomes is to be accomplished within the established 15-year timeframe. The five-year plan is available from: Human Genome Management Information System, Oak Ridge National Laboratory; Oak Ridge, TN 37831-6050, telephone (615) 576-6669. BACKGROUND A major long-term goal of the Human Genome Program is to identify all the genes and regulatory functions encoded in the three billion base pairs of human DNA. The first step in this process is to assemble detailed genetic and physical maps of the human genome. Subsequently, the complete sequence of human DNA must be determined. In order to attain this second objective, DNA sequencing technology must be further developed so that the cost will be significantly decreased and the rate significantly increased. In 1990, the cost of sequencing performed by highly skilled researchers in laboratories devoted to DNA sequencing was estimated to be about $2 to $5 per finished base. To stimulate the necessary technology development, NCHGR will provide support for innovative and high-risk projects that attempt completely new approaches, and those projects that propose significant improvements in available technology. The NCHGR already supports several projects designed to make improvements in current gel-based methods, to apply current methods to large-scale pilot projects, and to develop new approaches to DNA sequencing. Although progress is being made in these areas, there is a strong need to accelerate the pace. The purpose of this Request for Applications (RFA) is to stimulate investigation of totally new approaches, and approaches that have the potential to make revolutionary advances in current gel-based techniques. Thus, high-risk projects that are based on sound scientific principles are encouraged. RESEARCH SCOPE Applications are encouraged that address: o the development of new sequencing methods that will allow large-scale sequencing of DNA at a cost significantly below 50 cents per base pair, or o the improvement of, by at least ten-fold, current methods that are applicable enough for large-scale DNA sequencing. Applications to pursue DNA sequencing projects using state- of-the-art techniques will not be considered responsive to this RFA. Applications that are solely directed toward informatics, e.g., development of software and data bases to support large-scale sequencing projects, or development of algorithms and analytical tools to interpret genomic information, must be submitted under program announcement, "Mapping, DNA Sequencing, and Technology Development in Support of the Human Genome Program," PA-90-20, published in the NIH Guide for Grants and Contracts on July 27, 1990, Vol. 19, No. 28. Applications are particularly encouraged from scientists, such as engineers and physicists, and institutions, such as for-profit institutions and biotechnology companies, that have not traditionally requested research support from the NCHGR. Applicants whose expertise is primarily non-biological are especially encouraged to interact closely with biologists during the development of the research plan. Applications from minority investigators and women are encouraged. MECHANISM OF SUPPORT Support for this program will be through the Pilot Projects/Feasibility Studies (R21) and Traditional Research Grant (RO1) mechanisms. The R21 mechanism is used to support highly creative approaches for which substantial preliminary data are not yet available. R21 awards will be limited to $100,000 direct costs per year and to a maximum of two years of support, although the funding limit may be waived under exceptional circumstances. R21 grants are non-renewable. Other mechanisms, including the Research Program Project (P01) and Developmental Grants (P20), will also be considered when appropriate. The total amount of support available for grants under this RFA will be $2.0 million (direct and indirect costs) for the first year of the project and is contingent upon appropriation of funds for this purpose. It is anticipated that approximately five to ten awards will be made, representing a mix of research topics and mechanisms. This number may be increased if a large number of highly meritorious applications are received and if funds are available. The number of awards made will be contingent upon the quality of applications received and the availability of funds. ELIGIBILITY Domestic universities, medical colleges, hospitals, corporations and other public, private, and for-profit research institutions, including State and local government units, are eligible. Collaborations between scientists in academia and industry are especially encouraged. LETTER OF INTENT Applicants are asked to submit a letter of intent by January 31, 1991. This letter is to include a descriptive title of the proposed research, names of the Principal Investigator and other key investigators and their institutions. The letter of intent is requested in order to provide an indication of the number and scope of applications to be reviewed and does not commit the sender to submit an application, nor is it a requirement for submission of an application. Letters of intent are to be sent to: Robert L. Strausberg, Ph.D. Program Director, Technology Development Program National Center for Human Genome Research Building 38A, Room 610 Bethesda, MD 20892 Telephone: (301) 496-7531 E-mail: CXR@NIHCU.BITNET; CXR@CU.NIH.GOV REVIEW PROCEDURES Applications in response to this announcement will be reviewed in accordance with the customary NIH peer review procedures. Simultaneous submission of identical applications to different NIH solicitations is not allowed, nor can essentially identical applications be reviewed by different initial review groups. Therefore, if the application submitted in response to this RFA is identical to or substantially the same as one already submitted to the NIH, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Similarly, an application that is essentially identical to one that has already been reviewed cannot be submitted in response to this RFA. This does not preclude the submission of a previously reviewed application that has undergone substantial revision; however, such an application must address, in the Introduction, the previous critique. Applications will be screened for responsiveness to this RFA by NCHGR staff. Any application deemed non-responsive will be returned to the applicant or referred to the Division of Research Grants (DRG) for reassignment as an unsolicited application according to DRG referral guidelines at the discretion of the applicant. If a large number of responsive applications is received, a preliminary peer review will be organized by the Office of Scientific Review, NCHGR, to identify the most meritorious applications. Applications that are deemed non-competitive by this process will receive only a brief critique, will not be reviewed further, and the applicant will be notified. The remaining applications will be reviewed for scientific and technical merit by the Genome Research Review Committee or another appropriately constructed review committee within the NCHGR. Review criteria will include the following: o Originality and innovativeness of the approach including supporting background documentation explaining the evolution of the proposed approach; o Feasibility of the research as demonstrated by a well-developed, detailed experimental design. In all cases, but particularly when sufficient preliminary data are not available, careful attention must be paid to potential pitfalls in the experimental design. The investigator must detail the plans to address such problems or pitfalls; o Overall scientific and technical merit of the research; o The potential of the proposed work to attain the research objectives outlined in this RFA; o Training, experience, research competence, and dedication of the investigator(s); o Adequacy of available facilities; o Provision for the protection of human subjects and the humane care of animals; and o Appropriateness of the requested budget for the work proposed. AWARD CRITERIA Applications will compete for funds set aside for this purpose. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review; o Value of the research for achieving the goals of the Human Genome Program; o Balance among research goals with respect to the NCHGR grant portfolio; o Availability of funds. METHOD OF APPLYING Applications must be submitted using the form PHS 398 (rev. 10/88). The RFA label available in the revised application kit MUST be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. Application kits are available in the business or grants office at most academic or research institutions, and from the Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441. Because of the specialized interest of this NCHGR program, and the potential for overlap with other NIH programs, it is strongly recommended that potential applicants contact NCHGR staff to discuss research objectives and appropriate mechanisms. Applications will be accepted in accordance with the following schedule: TIMETABLE Letter of Intent (optional): January 31, 1992 Receipt Date: March 17, 1992 IRG Review: June 1992 Council Review: September 1992 Earliest Funding Date: September 30, 1992 It is essential that applicants type "DNA Sequencing Technology Development in Support of the Human Genome Program" and the RFA number, HG-92-01, on line 2 on the face page of the application form. The original and four copies of the application must be submitted to: Grant Application Receipt Office Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892 To expedite the review process, it is also important to simultaneously submit two copies of the application directly to: Office of Scientific Review National Center for Human Genome Research National Institutes of Health Building 38A, Room 604 9000 Rockville Pike Bethesda, MD 20892 INQUIRIES Prospective applicants are encouraged to contact the staff members very early in the planning phase of the application. For more information regarding specific research areas or mechanisms, contact: Robert L. Strausberg, Ph.D. Program Director, Technology Development Program National Center for Human Genome Research Building 38A, Room 610 Bethesda, MD 20892 Telephone: (301) 496-7531 E-mail: CXR@NIHCU.BITNET; CXR@CU.NIH.GOV For information about PHS grants policy, applicants may contact: Ms. Alice Thomas Chief, Grants and Contracts Management Branch National Center for Human Genome Research Building 38A, Room 613 Bethesda, MD 20892 Telephone: (301) 402-0733 The program and grants management officials welcome the opportunity to clarify any issues or questions related to this RFA and encourage written and telephone inquiries. AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.172. Awards will be made under the authority of the Public Health Service Act, Sections 301 (Public Law 78-410, as amended 42 U.S.C. 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirement of Executive Order 12372 or to Health Systems Agency review.