Tools for genetic and genomic studies in emerging model organisms.

This Program Announcement (PA) is to encourage investigator-initiated applications for research designed to generate genetic tools and genomic resources that will enable researchers to exploit the full potential of novel or developing model systems for comparative and functional genomic studies. The typical model organism to be considered should have a publicly available draft of the genomic DNA sequence with a minimum of 5X coverage. In addition, it should have at least one of the following characteristics: shows promise as, or is, a model for basic biological or behavioral mechanisms; occupies an important evolutionary niche that may yield novel insights in comparative studies; or has potential as, or is, a model for developmental or disease processes. Applicants are expected to ensure that reagents, technologies, and resources developed tinder this initiative are made widely available to the research community.

This PA is not intended to encourage genome sequencing projects or studies of model organisms for which there are well-established databases and other genome-related resources, e.g, mouse, Drosophila, C degans, and S. cerevisiae. In general, resources to study organisms that fit primarily within the mission of another National Institutes of Health (NIH) Institute or Center, such as pathogenic microorganisms, are not encouraged through this PA.

The advent of the genomic era has been a boon for the investigation of a growing number of model organisms. Completion of DNA sequencing of each genome presents opportunities for novel insights into genomic function, the regulation of gene expression, and evolutionary processes. Yet, the large scale of many sequencing projects and the sheer volume of sequence data create a considerable challenge for the individual investigator as well as consortia of researchers to obtain the resources and tools required to make maximal use of genomic information for comparative or functional studies.

The major goal of this PA is to support research that will enhance the usefulness of DNA sequence information for newly emerging or developing model organisms for which there are limited genomic resources. Objectives to be addressed in applications submitted in response to this PA include, but are not limited to, the following: 1) improvements in tools for mining of data for genomes having unique composition or structure; 2) improved database management and integration with other databases (requests for the maintenance of databases alone are not encouraged); 3) generation of comprehensive cDNA libraries; 4) development of microarray reagents and/or services; 5) improved methods for linking expression arrays with standard phenotypes or with specific biological or behavioral outcomes; 6) development of novel approaches for mutagenesis and for rapid identification and characterization of point mutations; 7) development of novel transposable element-based techniques for the generation of knockouts or other mutations; 8) improvements in gene transfer technology and in vectors for genomic manipulation; and 9) generation of sets of gene knockouts or knock-downs.

This PA will use the NIH research resource grant (R24) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this PA may not exceed four years. A maximum of $250,000 direct costs (exclusive of subcontractual indirect costs) per year will be provided.

This PA uses just-in-time concepts, it uses the non-modular budgeting format. Follow the instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/ NIHGPS_Part2.htm.

The NIH is interested in ensuring that the research resources (constructs, reagents, cell lines, software tools, expression data, methods, etc.) developed through this PA become readily available to the research community for further research, development, and application, in the expectation that this will lead to products and knowledge of benefit to the public. At the same time, NIH recognizes the rights of grantees to elect and retain title to subject inventions developed under federal funding tinder the provision of the Bayh-Dole Act.

This PA has two special requirements regarding research resources produced in proposed projects: 1) Applicants are required to include in their applications a specific plan by which they will share research resources with the wider scientific community. A reasonable rime frame for periodic deposition of mutants, reagents, and data should be specified in the application. 2) Applicants are required to include a plan addressing if, or how, they will exercise their intellectual property rights while making available to the broader scientific community, patentable research resources. The plan should address the following questions: Will material transfers be made with no more restrictive terms than in the Simple Letter Material Transfer Agreement or the Uniform Biological Material Transfer Agreement? Will there be reach-through requirements on materials transferred? Should any intellectual property arise that requires a patent, will the technology remain widely available to the research community?

Both the sharing and intellectual property plans should, at a minimum, address these elements in a clear and concise manner. Applicants are encouraged to inform and/or confer with their institutional offices of technology transfer to develop plans for addressing these requirements.

Applicants are reminded that the grantee institution is required to disclose each subject invention to NIH within two months after the inventor discloses it in writing to grantee institutional personnel responsible for patent matters. The awarding Institute reserves the right to monitor awardee activity in this area to ascertain if patents or patent applications are adversely affecting the goals of this PA.

Applications must be prepared using the PHS 398 research grant application instructions and forms trey. 5/2001). Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal identifier when applying for federal grants or cooperative agreements. The DUNS number can be obtained by calling 866-705-5711 or through the web site at http://www. dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 is available at http://grants.nih.gov/grants/funding/pbs398/ phs398.html in an interactive format. For further assistance contact GrantsInfo, 301-435-0714, e-mail: [e-mail]. The title and number of this PA must be typed on line two of the face page of the application form and the YES box must be checked.

In the background section, the applicant should include a description of existing publicly available resources for the model organism being studied. The applicant should define how the proposal will enhance available resources and provide evidence of research community consultation and consensus regarding the potential value of the resource. In a brief section following the research plan, the applicant must describe plans to share research resources and to exercise intellectual properly rights

Applications submitted in response to this PA will be accepted at the standard application deadlines, which are available at http:/grants.nih.gov/ grants/dates.htm. Application deadlines are also indicated in the PHS 398 application kit.

Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to: Center for Scientific Review (CSR), NIH, 6701 Rockledge Drive, Room 1040, MSC 7710, Bethesda, MD 20892-7710 USA; Bethesda, MD 20817 (for express/courier service).

Applications must be mailed on or before the receipt dates described at http://grants.nih.gov/ grants/funding/submissionschedule.htm. The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an unfunded version of an application already reviewed, but such application must include an introduction addressing the previous critique.

Contact: Anthony Carter, Division of Genetics and Developmental Biology, National Institute of General Medical Sciences (NIGMS), Building 45, Room 2AS-25R, MSC 6200, Bethesda, MD 20892-6200 USA, 301-594-0943, fax: [phone], e-mail: [e-mail].

Reference: PA No. PA-04-141