Large-Scale Phenotypic Drug Screening

Zebrafish are well-suited to large-scale genetic and chemical discovery paradigms. Accordingly, we developed a customized robotics-enabled platform, termed automated reporter quantification in vivo (ARQiv), enabling phenotypic screening of zebrafish larvae at true high-throughput rates (e.g., 20,000 per day). Using this platform, we recently identified drug candidates that protect rod photoreceptors in fish and mouse models of retinal degeneration. We also used this platform to show that chemically modulating microglia reactivity can enhance retinal regeneration kinetics, implicating retinal microglia as critical regulators of retinal regenerative potential.

In collaboration with Dr. Valeria Canto-Soler and colleagues, we adapted the ARQiv platform to human induced pluripotent stem cell (hiPSC)-derived organoid disease models. More recently, we received a high-end instrumentation grant to update the ARQiv platform, adding a high-content imaging component and adaptable microfluidics system to facilitate screening of any HTS-compatible model system. This newly minted “ARQiVST” platform anchors a High-throughput Phenotypic Screening (HPS) core facility that affords unique training opportunities in cross-species phenotypic screening based discovery of genes and drugs targeting conserved mechanisms of pathogenesis in living and complex three-dimensional disease models.