Genomics Core

Research Inst Of Fox Chase Can Ctr, Philadelphia PA

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY/ABSTRACT - GENOMICS CORE The goal of our Program is to fill a critical gap in knowledge in understanding the molecular mechanisms that control the development of human and mouse γδ T cells. To achieve this goal, the Projects within our Program employ a variety of cutting-edge genomics approaches at both the bulk population and single cell level to uncover the regulatory axes that govern γδ versus αβ lineage development. The Genomics Core leverages the genomics expertise of Core Director Dr. Ciofani, who together with bioinformatics collaborator Dr. Timothy Reddy, is uniquely positioned to provide standardized assay and analytical support for RNA-seq, ChIP-seq, CUT&RUN, ATAC-seq, in addition to single cell genomics (e.g. CITE-seq, TCR repertoire analysis, scATAC-seq, and multiomics). With the anticipated development of new genomics modalities and capabilities, the Genomics Core will also continue to develop new computational pipelines to keep pace with technological advances. In particular, the Core will establish bioinformatic tools for a novel single cell high-throughput reporter activity assay (scSTARR-seq) developed by Project 2 and applied to both human and mouse models (Projects 1, 2, 3) to identify the cis regulatory network (enhancers and silencers) targeted downstream of strong versus weak TCR signals. Moreover, the Genomics Core will integrate data from multiple orthogonal modalities (i.e. gene expression, chromatin accessibility, and enhancer reporter activity) to generate regulatory networks for human and mouse γδ T cell lineage specification. This will facilitate comparative genomics analysis aimed at defining the shared and divergent regulatory features of mouse and human γδ lineage development. Altogether, the main objectives of the Genomics Core are (1) training in genomics approaches and bioinformatics analysis, (2) performing genomics experiments and NGS sequencing of libraries to complete Project Aims, (3) bioinformatic analysis of global and single cell genomics assays, (4) standardization of experimental and analytical methods, and (5) facilitating data sharing and accessibility. Taken together the training, experimental, and bioinformatic efforts of the Genomics Core will facilitate an unprecedented understanding of γδ versus αβ lineage commitment and provide a valuable resource for the field.