Strategies for Germ-Line Modification in the Rat.

Seven centers and institutes of the NIH invite applications to establish methods for the efficient production of rat models that contain germ-line mutations that will facilitate the transfer of biological concepts to human health problems. Development of rat embryonic stem cell (ESC) technology by modification of current techniques or development of new approaches will meet the needs of researchers using the rat to study human health and disease. This initiative is designed for rat models only and should not include human subjects or tissues.

Examples of research topics that could be addressed under this program announcement are 1) strategies for culturing pluripotent rat ESCs to allow genetic manipulation and to create rats with germ-line transmission of genetic modifications, 2) development of alternative technologies to create null mutations or gene replacement in the rat, 3) development of cost-effective nuclear transfer procedures in the rat, 4) studies that demonstrate mutation transfer to rat stem cells or other cells for transfer into embryos or germ cells, and 5) methods for targeting engineered introns into rat chromosomal DNA to support the study of gene function.

This program will use the NIH Research Project Grant (R01) mechanism. The total project period may not exceed five years. For all competing R01 applications requesting up to $250,000 per year in direct costs, 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.

Prospective applicants are asked to submit a letter of intent by 1 September 2001. Final applications are due 1 October 2001. More information on this announcement is available on the Internet at http://grants.nih.gov/grants/guide/ PAR-01-077.html.

Contact: John D. Harding, Division of Comparative Medicine, National Center for Research Resources, 6705 Rockledge Drive, Suite 6050, MSC 7965, Bethesda, MD 20892-7965 USA, 301-435-0776, fax: [phone], e-mail: [e-mail]; Judy Mietz, Division of Cancer Biology, National Cancer Institute, 6130 Executive Boulevard, EPN 5032, Bethesda, MD 20892 USA, 301-496-7028, fax: [phone], e-mail: [e-mail]; Martha S. Lundberg, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Rockledge II, Room 9146, Bethesda, MD 20892-7940 USA, 301-435-0513, fax: [phone], e-mail: [e-mail]; Mary Lou Oster-Granite, Mental Retardation and Developmental Disabilities Branch, National Institute of Child Health and Human Development, 6100 Executive Boulevard, Room 4B-09, MSC 7510, Bethesda, MD 20892-7510 USA, 301-435-6866, fax: [phone], e-mail: [e-mail]; Arlene Y. Chiu, Repair and Plasticity Program, National Institute of Neurological Disorders and Stroke, Neuroscience Center, Room 2206, 6001 Executive Boulevard, Bethesda, MD 20892 USA, 301-496-1447, fax: [phone], e-mail: [e-mail]; Nancy L. Nadon, Biology of Aging Program, National Institute on Aging, 7201 Wisconsin Avenue, GW 2C231, Bethesda, MD 20892 USA, 301-496-6402, fax: [phone], e-mail: [e-mail]; Jonathan D. Pollock, Genetics and Molecular Neurobiology Branch, Division of Neuroscience and Behavioral Research, National Institute on Drug Abuse, 6001 Executive Boulevard, Rockville, MD 20892 USA, 301-435-1309, fax: [phone], e-mail: [e-mail]. Reference: PA No. PAR-01-077