Translating Duke Health Faculty Candidate Seminar
Xin Jin, PhD, is visiting from Harvard to give her talk "In vivo Perturb-seq: study gene function at scale."
Abstract: The thousands of disease risk genes and loci identified through human genetic studies far outstrip our current capacity to systematically study their functions. I will discuss our attempt to develop a scalable genetic screen approach, in vivo Perturb-Seq, and apply this method to the functional evaluation of 35 autism spectrum disorder (ASD) de novo loss-of-function risk genes. Using CRISPR-Cas9, we introduced frameshift mutations in these risk genes in pools, within the developing brain in utero, and then performed single-cell RNA-Seq in the postnatal brain. We identified recurrent and cell type-specific gene signatures from both neuronal and glial cell classes that are affected by genetic perturbations, and pointed at elements of both convergent and divergent cellular effects across many ASD risk genes. In vivo Perturb-Seq pilots a systems genetics approach to investigate at scale how diverse mutations affect cell types and states in the developing brain, and can be used in various in vivo and in vitro model organisms and systems. I will also briefly discuss my future research interests including comparative studies on glial development as well as investigating mechanisms of how hormonal physiology shapes neurodevelopment and brain functions.