Metals in Medicine.

The objective of this program announcement (PA) is to encourage research that bridges the areas of inorganic chemistry and medicine. The mechanisms by which organisms control transition metal ions and the roles of these metals in cellular regulation and cell--cell signaling are of primary interest. The interactions of synthetic inorganic complexes with living systems and their components are a second area of interest. These areas are linked by the need to involve researchers having a deep understanding of inorganic chemistry with state-of-the-art problems in biomedical research. Much of the work is expected to involve collaborations between chemists and biochemists and cell and molecular biologists. The results will be relevant to understanding the mechanisms of metal toxicity and the basic cellular roles underlying the nutritional requirement for essential metals. It is expected that this research will also contribute to the identification of new targets for drug discovery, diagnostics, and future therapeutic approaches, although drug development per se is not a focus of the program at this time.

The emphasis of this PA is on the ions, complexes, and organometallic compounds of the transition metals, posttransition metals, and metalloid elements. Based on input from a broad scientific community, the NIH held a meeting titled "Metals in Medicine: Targets, Diagnostics, and Therapeutics" on 28-29 June 2000. Based on this meeting and other sources of information, the institutes involved seek to stimulate additional applications in the areas of emerging areas of metal metabolism and regulation, and interactions of metal complexes with living systems.

A goal of this PA is to utilize the power of inorganic chemistry to provide new knowledge of biological systems. Another goal is to improve understanding of the reactions of metal complexes in living systems to improve the specificity of these interactions and gain control over the potential toxicity of synthetic metal complexes. The long-term goal is to establish the basic principles of an inorganic medicinal chemistry that will allow for rational design and screening of potential metallopharmaceuticals in the future.

The NIH Metals in Medicine meeting report at http://www.nigms.nih.gov/news/meetings/metals.html includes a list of specific research opportunities and challenges. This list is intended to be illustrative, not exhaustive. Investigator-initiated ideas are welcome on any subject that will contribute to the objectives of this PA. Full details of this solicitation can be found on the Internet at http://grants.nih.gov/grants/guide/ pa-files/PA-01-071.html.

This PA will use existing NIH research project grant (R01), but some research efforts may be more appropriate for the Program Project (P01) grant mechanism or the Resource-Related Research Project (R24) grant mechanism. Investigators interested in applying for P01 or R24 grants should contact the institute program staff listed at the end of this announcement.

Contact: Peter C. Preusch, Division of Pharmacology, Physiology, and Biological Chemistry, National Institute of General Medical Sciences, Building 45, Room 2AS.43C, Bethesda, MD 20892-6200 USA, 301-594-5938, fax: [phone], e-mail: [e-mail]; Maren R. Laughlin, Metabolism Program, National Institute of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Boulevard, Room 6101, MSC 5460, Bethesda, MD 20892-5460 USA, 301-594-8802, fax: [phone], e-mail: maren.laughlin@ nih.gov; Claudia Thompson, NIEHS, DERT/ PD/CEMBB, MD EC-21, PO Box 12233, Research Triangle Park, NC 27709 USA, 919-541-4638, fax: [phone], e-mail: thompso1@ niehs.nih.gov; Becky Costello, Office of Dietary Supplements, NIH, Building 31, Room 1B25, Bethesda, MD 20892 USA, 301-435-3920, fax: [phone], e-mail: [e-mail]. Reference: PA No. PA-01-071