Vera-Choqqueccota, S. (BMEB) – A CRISPRi-Based platform for multimodal functional analysis of neurodevelopmental and neuropsychiatric disorders risk genes in engineered mouse cortical neurons

Neurodevelopmental and neuropsychiatric disorders (NPDs), such as autism spectrum disorder and schizophrenia, are among the most heritable yet mechanistically complex conditions. While large-scale genomic studies have identified hundreds of high-confidence risk genes, the lack of scalable and integrative platforms has limited our ability to functionally characterize these genes. To address this, I am developing a CRISPR interference (CRISPRi)-based screening platform using mouse embryonic stem cells (mESCs) engineered to express Ngn2 for rapid and standardized neuronal differentiation and dCas9-KRAB for gene repression. In Aim 1, I will generate and validate this cell line, enabling reproducible and scalable perturbation of disease-relevant genes. In Aim 2, I will apply this system to characterize the effects of knocking down ten NPD-risk genes using multimodal analysis of morphology, transcriptomics, and electrophysiology. In Aim 3, I will build a framework to crowdsource functional analysis of NPD risk genes to design gRNAs, access experiments remotely, and analyze data using simplified, accessible tools. Together, this project advances both scientific understanding of NPD mechanisms and equitable access to functional analysis.

Event Host: Samira Vera-Choqqueccota, PhD Student, Biomolecular Engineering & Bioinformatics

Advisor: David Haussler