SUMMARY The overall objective of the Basic Science Core I (BSCI) is to provide in vitro shared resources and training to basic and clinical researchers studying HIV-1 induced neurological disorders at the molecular and cellular levels, and initiate translational research toward better understanding of disease mechanisms and discovery of reliable biomarkers for early diagnosis and development of intelligent therapies toward cure. It is now clear that the current antiretroviral therapy (ART) effectively controls viremia in virtually all HIV-1 patients, but fails to eliminate HIV-1 from latently infected cells including T-cells, macrophages, brain microglial cells, and cells in other sites of latency throughout the body. As such, patients remain at risk for rapid viral rebound upon interruption of ART. New strategies are needed to ablate the virus from latently infected cells and/or identify and destroy latently infected cells. The BSCI is designed to provide investigators with intellectual and technical expertise along with cellular and molecular tools to initiate research for understanding mechanisms of HIV- 1/CNS disease and the development of cell and virus based strategies toward control and elimination of HIV-1 infection in the CNS. The cell culture facility of BSCI provides investigators with well characterized highly purified cells prepared from brain including neurons, astrocytes, oligodendrocytes, microglia, and endothelial cells, as well as cultured peripheral blood cells for performing molecular, cellular, and virological studies toward virus-host interaction, assessing efficiency of the methodologies for elimination of latently infected cells and virus, and high throughput approaches toward identification of biomarkers. The BSCI also provides state-of- the-art services for discovering the molecular mechanisms involved in the development of AIDS-associated CNS dysfunction through proteomics/metabolomics and data analysis. Novel methods for discovering biomarkers, innovative differential expression profiling and bioinformatics, along with interactomics and phosphoproteomics are among the services that will be reliably and efficiently offered to investigators. The core's unique expertise in gene editing and gene delivery will be used to guide investigators in the development and implementation of effective strategies for introducing mutations in viral genes and host genes and implementing various techniques for assessing the efficacy and specificity of editing strategies and utilizing the most effective viral vectors including lentivirus, AAV, and adenovirus for delivery. 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 CNAC developmental award recipients and CNAC users in conducting productive high impact research in neuroAIDS.