Repurposing CRISPR to turn genes on and off

The ability to precisely manipulate gene expression enables exploration of gene function and establishment of causal relationships. I will discuss CRISPR tools for turning genes on and off from a research and therapeutics perspective. I will also describe advances in CRISPRi/a functional genomics technologies highlighting platforms that enable single cell functional genomics and mapping of genetic interactions (GI) in the context of environmental perturbations. Specifically, in five GI maps measuring ?250,000 GIs or higher-order environmental interactions, we discover widespread rewiring of relationships between genes, complexes, and ontologies across conditions. Specific bioprocesses drive the rewiring signal in each environmental state, as highlighted in our findings that the TIP60 and PP2A complexes radically alter their interaction profiles after inhibition of ATR. This resource reveals numerous genetic relationships for the fields of DNA damage signaling, DNA repair, and cell-cycle control and explores their context specificity. Our work advances a framework for using GI maps to explore environmental rewiring.

Speaker: Luke Gilbert, UC San Francisco