Innovative Use of Nonmammalian Model Organisms to Study Membrane Transport.

This initiative will provide R21 pilot and feasibility grants to use nonmammalian models to develop reagents, methodologies, and novel approaches to the study of membrane transport, especially those membrane transport processes involved in diseases of relevance to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and those involved and required for normal cell function of interest to the National Institute of General Medical Sciences (NIGMS).

Examples of relevance to the NIDDK include new highly differentiated cell lines (such as tubule cells), mutant organisms, electrophysiologic or imaging methods to study transporter physiology and regulation in vivo, structure-function studies of purified homologous proteins or proteins in model membrane systems, identification of human homologues to proteins studied in model organisms, and the search for novel genes and proteins involved in membrane transport of ions and nutrients. Examples of interest to the NIGMS include new vectors for the overexpression of membrane transporters and associated membrane proteins, refolding and purification strategies of overexpressed transporters, and novel structural approaches to the elucidation of their structures.

The following are some examples of the types of investigations that would be responsive to this request for applications: 1) new strategies for finding novel transporters and their associated molecules; 2) development of isolated cell preparations and cell lines (such as renal tubule cells) from genetically tractable nonmammalian model organisms, especially those with sequenced genomes; 3) development of forward and reverse genetic strategies for characterizing membrane protein structure, function, and regulation; 4) finding new means of utilizing mutant organisms for the study of membrane transport; 5) use of model organisms to study changing roles of transporters throughout development and among organs; 6) finding homologues of important mammalian genes that are more easily overexpressed and/or crystallized; 7) development of new methods that will lead to the characterization of ion channels and other ion transporters and their interacting proteins; 8) development or refinement of electrophysiologic, electron microscopic, or imaging methods to be used for assessing membrane transport function in the intact organism; and 9) development and application of informatic tools for identifying membrane transport proteins and studying their function.

It is anticipated that, as a result of the grants funded with this request for applications, new and innovative approaches will have been developed and will be effectively utilized by the investigators to submit competitive investigation-initiated R01 research grant applications.

Prospective applicants are asked to submit a letter of intent by 22 February 2001, with final applications due 22 March 2001. Additional information is available on the Internet at http://grants.nih.gov/ grants/guide/rfa-files/RFA-DK-01-012.html.

Contact: M. James Scherbenske, Renal Physiology/Cell Biology and Kidney Centers Program Director, DKUHD, NIDDK, 6707 Democracy Boulevard, Room 613, Bethesda, MD 20892-5458 USA, 301-594-7719, fax: [phone], e-mail: [e-mail]; Maren Laughlin, Metabolism Research Program Director, DDEMD, NIDDK, 6707 Democracy Boulevard, Room 6101, Bethesda, MD 20892-5458 USA, 301-594-8802, fax: [phone], e-mail: [e-mail]; Michael K. May, DDND, NIDDK, 6707 Democracy Boulevard, Room 663, Bethesda, MD 20892-5458 USA, 301-594-8884, fax: [phone], e-mail: maym@ extra.niddk.nih.gov; Jean Chin, CBB, NIGMS, 45 Center Drive, Room 2AS 19A, Bethesda, MD 20892-6200 USA, 301-594-2485, fax: [phone], e-mail: [e-mail]. Reference: RFA No. DK-01-012