PROJECT SUMMARY/ABSTRACT The objective of this program project application is to gain insight into the molecular basis by which genome- wide remodeling of E box DNA binding protein activity, in response to TCR signals, controls the development and functional specialization of γδ T cells, which are critically important to host defense. In supporting this effort, the Genomics Core would provide centralized access to scRNA-Seq, ChIP-Seq, ATAC-Seq and HiC sequencing platforms to allow large-scale genomic location analysis of transcription factors as well as epigenetic marks to reveal and describe the chromatin landscapes of αβ and γδ T-lineage cells. The Genomics Core would generate robust single-cell transcriptomic and small-cell-number epigenetic datasets, epigenetic landscapes as well as methods to describe the folding patterns of human and murine αβ and γδ T-lineage cells in global terms. The Genomics Core would assist the participating laboratories for experimental design and work closely with the participating members of the program to analyze individual, as well as, combined data sets. The Genomics Core will also continue to generate new bioinformatics pipelines to process genome-wide data sets obtained from bulk populations as well as data obtained from single cells. Finally, in addition to the provision of core services, the Genomics Core would be a hub for the training of graduate students and postdoctoral fellows in the utilization of deep DNA sequencing and associated bioinformatics techniques for the participating laboratories.