Cell Biology and Functional Analysis Core for Institution # 269291

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SUMMARY The overall goal of the Cell Biology and Functional Analyses (CBFA) core is to provide basic scientists as well as clinical researchers studying HIV-1 induced neurological deficits at cell and molecular levels, resources, mentorship, and training. In addition, resources would be available to researchers transitioning to the area of NeuroHIV. Despite the success of the currently used antiretroviral therapy (ART) in controlling viral load in virtually all HIV-1 patients, this cocktail of viral inhibitors has not been able to eliminate the virus from latently infected cells including T-cells, macrophages, brain microglial cells, and cells in other sites of latency throughout the body. Therefore, the individuals remain at risk of viral rebound once they stop ART regimen. In the recent years, several strategies have been implemented to remove/edit viral sequences from the latently infected reservoirs. Equally as important is to be able to identify such cells to target and destroy them. The CBFA core is designed to provide investigators with training and technical expertise to utilize cellular and molecular tools to conduct research related to deciphering molecular mechanisms of HIV-1-induced CNS disease and ultimately design of molecular therapeutics to combat HIV-1 infection in the brain. This core would provide investigators with well characterized highly purified brain cells including neurons, astrocytes, oligodendrocytes, microglia, endothelial cells, and neural progenitors as well as cultured human peripheral blood cells for performing molecular, cellular, and virological studies. Moreover, human induced pluripotent stem cell (hiPSC) lines, and cortical spheroids and cerebral organoids from iPSCs, will be generated, characterized and made available for the core users in the field of NeuroHIV. In addition, expertise will be also provided for the isolation, characterization, propagation and maintenance of a variety of HIV-1 clades, HIV-2 and SIV. In this submission, we have included novel methods to study neuronal function in different regions of the brain using our Microelectrode Array (MEA) technology. In addition, expertise and training in microscopical, immunohistochemical analyses are offered to investigators. Our core will work closely with the other cores to promote a comprehensive multidisciplinary collaborative center program. This synergistic approach will ensure the success of CNHC developmental award recipients and CNHC users in conducting productive high impact research in neuroHIV. The main strength of our program is our team of experts with complementary expertise for investigators to conduct their neuroHIV research while working closely with the viral vector facility, and ultimately performing experiments in highly purified CNS cell cultures to assess the functional aspects of neuronal cells both in vitro and ex vivo.