Human genes associated with brain-related diseases are being discovered at an accelerating pace. A major challenge is to identify the mechanisms of action for these genes, and to determine potential therapeutic strategies. To elucidate these mechanisms in human cells, we established a CRISPR-based platform for genome-wide screens in human induced pluripotent stem cell (iPSC)-derived neurons, glia, and multi-lineage assembloids. Complex libraries of single-guide RNAs (sgRNAs) enable us to conduct genome-wide or focused loss-of-function (CRISPR interference, or CRISPRi) and gain-of-function screens (CRISPR activation, or CRISPRa). Such screens can reveal molecular players for phenotypes based on survival, stress resistance, fluorescent phenotypes, high-content imaging, and single-cell RNA-Seq. To uncover disease mechanisms and therapeutic targets, we are conducting genetic modifier screens for disease-relevant cellular phenotypes in patient-derived neurons and glia with familial mutations and isogenic controls. CRISPRi/a can also be used to model and functionally evaluate disease-associated changes in gene expression, such as those caused by expression quantitative trait locis (eQTLs), haploinsufficiency, or disease states of brain cells.
In this webinar, viewers will:
- Learn about CRISPRi and CRISPRa-based functional genomics in iPSC models of brain disease
- Discover CRISPR-based screens with single-cell RNA sequencing readouts
- Gain insight into identification of disease mechanisms and therapeutic targets for brain disease through CRISPR screens
- Have the opportunity to ask questions during the live broadcast.
This webinar will last for approximately 60 minutes.