This competing continuation application requests support to train three PhD scientists or post-resident physicians [MD or PhD/MD], holding positions at two partner institutions in India, for investigative careers in reproductive research. Emphasis will be placed on training in cell and molecular biology of reproduction with translational components aimed at infertility and the discovery of new leads for contraceptives. The global need for new options in contraception is highlighted by the fact that one in every two pregnancies is unwanted. Deployment of known contraceptives as well as advancement of new contraceptive options is a highest priority. This training program develops biomedical scientists who can meet the challenges of contraceptive discovery by equipping them with the tools to investigate the fundamental mechanisms governing reproductive processes, to recognize the opportunities afforded by such basic knowledge for identification of candidate contraceptive pathways and target molecules, and to test novel contraceptive strategies. Research and didactic experiences are tailored to accommodate trainees from diverse professional and academic backgrounds. Supplemental instruction is offered including courses in biostatistics, English for scientific purposes to improve writing and communication skills, recombinant DMA technology, structural genomics, pharmacology, bioethics, and drug discovery, design, synthesis, and selection. Interdisciplinary research training is achieved through interactions with preceptors who hold appointments in basic and clinical departments, through programs that evaluate leads and establish proof of principle of contraceptive action, and through collaboration with industrial advisors. All mentors hold faculty appointments in the School of Medicine or the College of Arts and Sciences and direct at least one active research grant. The institutional environment fosters interaction and exchange through a rich mix of seminars, visiting professors, conferences, and specialized research cores. The broad basic themes of faculty research programs include: the molecular analysis of sperm-egg fusion, signal transduction mechanisms between membrane receptors, sperm capacitation and the acrosome reaction, protein transcription, nuclear transcription factors, molecular physiology of ion channels, neuroendocrine control of mechanisms in reproduction, molecular control of spermatogenesis and oogenesis, autoimmunity to sperm antigens;sperm maturation in the epididymis, and circadian rhythms. Translational aims are fostered by faculty expertise in X-ray crystallography of reproductive proteins, mathematical modeling of ligand binding sites and organic synthesis of new small molecule inhibitors and the testing of their contraceptive action. Applied themes of this research include the development of male contraceptives targeted to transcription factors acting in the testis and epididymis, spermicides, infertility diagnostics, and contraceptive vaccines based on sperm and egg antigens. Continued training of basic scientists as well as internists, urologists, and obstetricians in cellular and molecular approaches to reproductive processes is consistent with the tradition and commitment to foster a close link between basic and clinical investigators at US institutions and their counterparts in India and to facilitate international cooperation and understanding.
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