This grant application requests funds to create a Center for Reproductive Research at Northwestern University. The Center will support a multidisciplinary group of scientists who will use innovative approaches toward an understanding of the mechanisms governing normal female fertility. The research focus of the Center will be to understand the structure-function relationships that exist between cells in the ovary and the hormones that regulate follicle maturation. The program is unique in its development of state-of-the-art biomaterials and advanced biophysical and structural approaches to achieve a more comprehensive understanding of ovarian function. The major hypothesis driving the proposed research is that normal follicle development depends upon the appropriate integration of signals derived from cell-cell contact and from the hormones and growth factors that are provided to the follicle structure in a cycle-dependent manner. Four projects will address this central hypothesis using innovative investigative strategies and a cohesive and highly effective partnership between basic biologists, structural biologists, chemical engineers, and clinical investigators. The projects that have been developed specifically for the Center include the derivation of an artificial three-dimensional environment in which individual oocyte-cumulus complexes can grow and to which endocrine factors can be applied; an investigation of the LH receptor and its role in follicular signal transduction pathways; an analysis of the interactions between ovarian co-activators, which are necessary for integrated gene activation and silencing; and the structural relationships between the follicle regulating hormones, inhibin and activin, and their signaling receptors. The rationale for creating such a Center is that elucidating the structure-function relationships between cells within the follicle and the hormones, receptors, and signaling molecules that control ovarian function will greatly advance our understanding of female reproductive physiology and thereby directly impact women's health.
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