Core--Biology

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This Program Project focuses on the role of CRF superfamily peptides and their binding proteins, receptors and modulators in the integration of endocrine, autonomic, behavioral and immune responses to stress. The first aim of this Program is to characterize physical interactions between CRF family ligands, their receptors and binding proteins and to define motifs required to activate downstream signaling events. The second aim is to explore the physiologic and pathophysiologic significance of these molecules at the cellular and system levels and to study the control of protein expression and secretion as well as modes of action. Addressing the questions of a complex ligand/receptor system is facilitated by the availability of key scientific tools. This core application is therefore designed to provide transgenic mice, antibodies, and immunoassays necessary to conduct the integrated studies proposed by the individual Projects. Transgenic mice overexpressing components of the CRF system, or null-mutant mice lacking one or more CRFRs and/or ligands, are essential for elucidating the physiologic roles of these ligands and receptors in normal development and in disease states. Detection and/or neutralization of gene products in vitro and in vivo are dependent on high affinity and high liter antibodies of appropriate specificity against CRF superfamily peptides and their soluble binding proteins and membrane bound receptors. Measurement of factors modulated by the CRF receptor-ligand system, including pituitary hormone ACTH and adrenal steroid corticosterone, are also required. This Core can provide transgenic mice, high quality antibodies and assay services that require highly trained personnel and specialized equipment which would otherwise be unavailable to individual projects due to high cost. The establishment of a Core permits reduced costs, improved quality control, efficiency, specialization of technical personnel, standardization of protocols and the dedication of equipment and space. Core B will be under the overall responsibility of Drs. K.-F. Lee (transgenic mice unit, 5% effort) and W. Vale (antibody production and assay services, 3% effort).