CORE 1: FUNCTIONAL GENOMICS SUMMARY The objective of the Functional Genomics Core (FGC) is to provide cuttingedge and innovative technologies for the functional characterization of the genome in a reliable, reproducible and costefficient manner. It will support Project 1 and Project 2 by facilitating proteomics experiments, including mapping of physical protein interactions, and CRISPR experiments, including mapping of genetic interactions. In particular, the FGC will perform mass spectrometry characterization, CRISPR gene editing, CRISPRi and CRISPRa screening, and provide expertise in data processing for these experimental platforms. This core will be comprised of three well established facilities: the Thermo Fisher Scientific Proteomics Facility for Disease Target Discovery located at the J. David Gladstone Institutes, the UCSD Institute for Genomic Medicine (IGM) Genomics Center and the UCSD Center for Computational Biology & Bioinformatics (CCBB). Additionally, we propose to create a new CRISPR screening core that leverages the Mali lab’s foundational expertise in genome engineering. The FGC core will be led by two pioneers in the fields of functional genomics, Drs. Krogan and Mali, who will employ stateoftheart techniques, many of which were developed or optimized in their respective labs. CoInvestigator Alan Ashworth, an internationally recognized expert in breast cancer genomics and one of the first to demonstrate the therapeutic promise targeting synthetic lethal interactions in cancer, will contribute expertise in target selection. Dr. Ashworth’s input will ensure that considerations of translational impact will be incorporated at all stages of experimentation. FGC technologies will be used extensively by Project 1 and Project 2. The FGC will not only enable Center investigators to accomplish the individual aims of this proposal, it will also serve as a resource to the wider scientific community by disseminating new assays and protocols.