Developing accessible in situ sequencing for optical pooled screening

Lead applicant: Chun Hao Wong, Milner Therapeutics Institute, University of Cambridge

Project overview

Optical pooled screening (OPS) combines CRISPR perturbations with high-content microscopy readouts such as morphology and subcellular localisation. Through leveraging in situ sequencing (ISS) methodology used in spatial transcriptomics, OPS enables association of individual cell with specific lentiviral guides within a pooled transduced population.  Since lentiviral pooled screening is standard in many labs, adding spatial resolution will provide a complementary high-throughput and cost-effective angle to study gene function. The FGx funding will enable further development on ISS workflows and address existing technical bottlenecks, thereby improving the accessibility of OPS for hypothesis generation and target discovery.