PROJECT SUMMARY/ABSTRACT The Emory CFAR Systems Immunology (SyImmun) Core (Core H) enables studies of the pathogenesis, treatment, and prevention of immunodeficiency virus infections in humans and nonhuman primates by providing access to state-of-the-art tools for the study of immunological function. There is a growing need for the application of advanced techniques that expand the HIV research community's ability to better understand immune cell function particularly given recent advances in high-dimensional analytic tools for the analysis of immune responses, including single cell RNA-Seq (scRNA-Seq) and related multi-omic techniques. The SyImmun Core comprises three Units: 1) Flow Cytometry; 2) Single Cell Multi-omics, and 3) Systems Immunology Training. The Core has an outstanding track record of providing CFAR Members with training, education, and a full range of services, including state-of-the-art polychromatic analytic flow cytometry and cell sorting, along with an array of analytic tools. Drawing on considerable expertise of Core leadership, the SyImmun Core will provide an array of high-throughput multi-omic single cell profiling techniques, including scRNA-Seq, CITE-Seq (Cellular Indexing of Transcripts and Epitopes, which allows integration of single cell transcriptomic and proteomic data), and single cell ATAC-Seq, which allows single cell epigenetic analysis. Training will be provided to investigators on the design of flow cytometric and single cell multi-omic experiments, along with a suite of courses that provide introductory and intermediate level courses in analytic tools used for the analysis of these data sets. Bioinformatic and biostatistical support and analytic tools will also be provided through the Core. The Systems Immunology Core proposes the following specific aims: Aim 1: Provide the highest quality flow cytometry data, cell sorting services, and analytic tools to Emory CFAR Members in support of groundbreaking Immunology research; Aim 2: Support an array of single cell multi-omics techniques, including scRNA-Seq, CITE-Seq and ATAC-Seq and outstanding bioinformatic and biostatistical expertise in collaboration with the Biostatistics and Bioinformatics Core; Aim 3: Train CFAR Members in the state-of-the-art design and analysis of flow cytometric and single cell multi- omic techniques. These services will provide Emory CFAR Members with unprecedented access to a wide range of tools in support of groundbreaking research to better understand immune function in HIV and SIV infection, and to further develop novel approaches to prevent and cure HIV infection.