CRISPR Core

PROJECT SUMMARY- CRISPR WHOLE GENOME SCREENING CORE (CSC) The goal of the proposed CRISPR Whole-Genome Screening Core (CSC) is to make state-of-the-art CRISPR- based technologies available to investigators in aging and geroscience to identify new genes and elucidate gene- specific events in mammalian cell-based model systems. High-throughput screens using CRISPR-based genomic libraries can identify novel genes in biological pathways that control aging and age-associated diseases by systematically knocking out individual genes in cultured cells and then measuring changes in cellular phenotypes. The CSC has accumulated the necessary expertise, instrumentation, software, and arrayed human and mouse whole-genome sgRNA CRISPR libraries to rapidly (~2-6 weeks) perform loss-of-function screens and make these capabilities available to the aging and geroscience research communities at an affordable cost. To our knowledge, these capabilities do not exist in the vast majority of universities or any other NSC. The CSC proposes three Specific Aims: (1) Work with investigators to design and develop robust, cell-based, aging- and age-associated disease-relevant assays suitable for high-throughput screening of whole-genome single-guide (sg) RNA CRISPR libraries, (2) Perform high-throughput CRISPR whole-genome loss-of-function screens using human and mouse-arrayed sgRNA CRISPR libraries and (3) Perform bioinformatic analyses, prioritize gene candidates and validate identified genes. Collectively, the services offered will uncover key signaling cascades, molecular pathways and biological processes driving the phenotypes of interest, ultimately advancing our understanding of complex biological systems and informing potential geroscience therapeutic interventions.