Development of Zebrafish Mutagenesis and Screening Tools.

This program announcement (PA) is intended to encourage investigator-initiated applications for research in using screening in zebrafish to detect and characterize genes, pathways, and phenotypes of interest in development and aging, organ formation, behavior, and disease processes. Applications that propose to advance the technologies associated with such phenotyping also are welcome. This PA is the result of a trans-NIH initiative, and awards will be made through the institute or center whose mission is most closely related to the proposed work.

The objective of this PA is to broaden the range, power, and utility of screens for new mutants of zebrafish. It will therefore support proposals for development of improved or novel methods for mutagenesis screens, as well as proposals for the actual execution of such screens. Methodology developed and data and mutants generated as a result of this PA are expected to be made widely available to the research community. Applicants must include as part of their applications a plan for disseminating these resources.

Objectives include but are not limited to 1) novel phenotypic screens for mutants (these screens may be based on observation of alterations in morphology, physiology, or behavior); 2) novel methods of mutagenesis (e.g., insertional); 3) genetic screens focusing on identifying mutations that affect the structure and function of specific tissue/organ systems; 4) screens focusing on identifying novel developmental genes and pathways, including those mediating sensitivity or resistance to environmental teratogens; 5) screens to analyze the genetic basis of adult phenotypes including behavior, aging, organ disease, cancer, and responses to environmental toxicants, alcohol, and drugs; 6) screens to detect altered gene expression patterns as a tool to identify components of genetic pathways or those altered by environmental agents; and 7) sensitized screens using strains carrying a known mutation to identify extragenic suppressors or enhancers of that mutation.

The participating NIH institutes and centers have provided a brief outline of their interests as they relate to the goals of this PA. These brief mission statements and other details of this solicitation are available on the Internet at http://grants. nih.gov/grants/guide/pa-files/PA-01-070.html.

For all competing applications requesting up to $250,000 direct costs per year, specific application instructions have been modified to reflect "modular grant" and "just-in-time" streamlining efforts being examined by the NIH. Complete and detailed instructions and information on modular grant applications can be found at http://grants. nih.gov/grants/funding/modular/modular.htm. Applications that request more than $250,000 in any year must use the standard PHS 398 (rev. 4/98) application instructions. Applications will be accepted at the following receipt dates: 1 July 2001 and 1 November 2001.

Contact: Written and telephone inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. A complete listing of contacts for both programmatic and fiscal/administrative inquiries may be found at http://www.nichd. nih.gov/PA/Zebrafish_Mutagenesis.htm. Reference: PA No. PA-01-070