CORE 2: TECHNOLOGY CORE SUMMARY The objective of the Technology Core is to provide cutting-edge and innovative technologies for the functional characterization of the genome and proteome in a reliable, reproducible, and cost-efficient manner. It will support Project 1 and Project 2 by facilitating proteomics, genetic interaction, and structural protein characterization experiments. In particular, the Technology Core will perform mass spectrometry characterization of host-pathogen protein-protein interactions (PPIs) and infection induced signaling network rewiring, CRISPR gene editing, and structural characterization by x-ray crystallography, cryo-electron microscopy (cryo-EM), and cross-link mass spectrometry (XL-MS). 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 UCSF Molecular Structures Group core facility located at the Mission Bay Campus of UCSF, and the Keck Advanced Microscopy Laboratory located at the Mission Bay Campus of UCSF. Additionally, we propose to create a new Functional Genomics Core (FGC) that leverages the Marson and Krogan lab’s expertise in genetic interaction mapping and genome engineering. The Technology Core will be led by pioneers in their respective fields, and who will employ state-of-the-art techniques, many of which were developed or optimized in their respective labs. The technologies described here will be used extensively by Project 1 and Project 2 investigators to accomplish the individual aims of this proposal, and will also serve as a resource to the wider scientific community by disseminating new assays and protocols.