The aim of this core to provide reagents and expertise and to perform a number of assays pertaining to signal transduction and apoptosis as applied to HIV research. Signal transduction at the core of a cell response to its environment, the regulatory pathways modified by HIV warrants further investigation in order to elucidate the underlying molecular mechanism responsible for the pathologies associated with infection. The modulation of susceptibility of host cells to HIV replication by the manipulation of these pathways could potentially lead to novel avenues of therapy. Apoptosis impacts many aspect of viral pathogenesis and assessing its role in HIV disease is crucial. We will provide apoptosis assessment to ongoing trials conducted by HIV clinicians. The elucidation of important components contributing to the attrition of CD4+ T cells can be evaluated by providing this quantification of apoptosis service. Developing assays and acquiring all the necessary expertise to embark in projects related to HIV signal transduction and apoptosis is very time consuming. Analysis of both apoptosis and certain signal transduction pathways and its role in HIV pathogenesis requires a multi-disciplinary approach and the service provided will help integrate the different perspectives and systems used by the proposed and anticipated CFAR users to broaden and investigate further the role of apoptosis and certain signaling pathways in HIV disease. Signal transduction and apoptosis analyses will require the generation of unique reagents. For this purpose, a number of the reagents will be synthesized by a core service located at the La Jolla Immunology and Allergy Institute under the direction of Dr. Carl Ware. Reagents for HIV research will be produced upon request. The objectives of the core are to: 1. Provide reagents and expertise for all aspects relating to apoptosis. 2. Provide reagents and expertise for all aspects of signal transduction pathway analysis especially those associated with HIV-1 chemokines, TNF family members, CD4 and TcR transduction pathway.
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