Genetic and genomic analyses of xenopus.

For the past few years, the international research community has been generating genetic and genomic data and reagents for the model systems, Z tropicalis and X. laevis. These products include: 1) cDNA libraries and EST sequences; 2) UniGene clusters; 3) full-insert cDNA clones and sequences; 4) a genetic map; 5) genomic libraries and genomic sequences; 6) a physical map; 7) genome sequence; 8) microarrays, and 9) transgenic and mutant animals (see http://www.nih.gov/science/models/xenopus). These diverse data and reagents are being generated by investigators from several different research communities, including geneticists, gene sequencers, gene mappers, cell biologists, developmental biologists, and bioinformatics experts. These materials and data can now be used to enhance the role of Xenopus as a model system. This PAR solicits applications from investigators in these different fields to combine these data, reagents and methodologies to elucidate the genetic basis of cell biological events, including embryonic development and organogenesis.

The PAR solicits applications to utilize the newly generated methodologies and reagents, such as the dones and sequence information, to identify and characterize genes, gene families, and gene networks that control developmental and cellular events. It also solicits applications to generate research tools and to perform pilot studies. Additionally, it solicits applications to devise and improve techniques to alter gene expression and to control the spatial and temporal pattern of gene expression.

Examples of projects include:

* Larger projects from multidisciplinary teams that are based on extensive preliminary data. These applications could use the newly available genetic and genomic data and reagents, and/or new methodologies to characterize and study genes involved in developmental events and in cellular processes. These projects will be particularly appropriate for collaborations between investigators with different expertise to analyze the genomic data to elucidate the genetic bases of cellular and developmental events.

* Smaller projects using existing techniques to generate research tools, such as genetic and physical maps, and to mine data; and projects to perform pilot studies such as phenotypic screens, microarray analyses, and expression cloning designed to produce preliminary data that would form the basis of future applications.

* Smaller projects designed to develop novel techniques, such as strategies for mutagenesis, conditional gene expression, or for identifying new genes or mutants, as well as new tools to mine and analyze sequence data:

Objectives to be addressed in applications submitted in response to this PA include, but are not limited to, the following: 1) development and/or application of novel methods of mutagenesis (e.g., insertional, site-specific, conditional knockout vectors or systems); 2) development and/or use of techniques supporting more efficient targeting of induced local lesions in genomes (TILLING); 3) development and/or use of technologies for gene inactivation and for gene expression manipulation including, but not limited to, morpholino oligonucleotides, new types of antisense technology, techniques for homologous recombination, techniques for gene trapping, and strategies for directing gene misexpression, or other transgenic methodologies; 4) development of high throughput small molecule screens; 5) development of new genetic or genomic resources that are of high priority for the Xenopus community; 6) development and/or application of novel screens for mutants. These may be refinements of phenotypic analyses preparatory to screening, or phenotypic screens based on observation of alterations in development, morphology, or physiology; 7) screens focusing on identifying novel developmental genes and pathways.

This funding opportunity will use the modular NIH Individual Research Project Grant (R01) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the nonmodular budget formats (see http://grants.nih.gov/ grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for nonmodular research grant applications.

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/ phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo at 301-435-0714 (telecommunications for the hearing impaired: TTY 301-451-0088) or by e-mail: [e-mail].

Applications must be prepared using the current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling 866-705-5711 or through the web site at hrtp://www.dnb.com/usL The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The letters of intent receipt dates for this PAR are December 19, 2005, 2006, 2007, with the application receipt dates January 18, 2006, 2007, 2008. The complete version of this PAR is available at http://grants/guide/pa-files/PAR-05-166.

Contact: Steven L. Klein, Developmental Biology, Genetics and Teratology Branch, National Institute of Child Health and Human Development, Room 4B01, 6100 Executive Boulevard, Bethesda, MD 20892 USA, Rockville, MD 20852 USA (for express/courier service; non-USPS service), 301-435-6886, e-mail: [e-mail]. Reference PAR-05-166