“Scalable investigation of gene function in vivo”
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 a panel of autism spectrum disorder (ASD) de novo loss-of-function risk genes. 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 addition, I will also briefly discuss the research directions in my lab, established in 2021, in applying molecular vector engineering and high content imaging approaches to study cell intrinsic and extrinsic effects of these disease risk genes. Our lab will use these systematic approaches, connecting genomic technology development with rigorous dissection of molecular mechanisms, to learn new insight about how complex inputs are integrated into the developing brain.
Xin Jin is an Assistant Professor in the Department of Neuroscience and core member of Dorris Neuroscience Center at Scripps Research. She was previously a Junior Fellow at Harvard Society of Fellows working with the groups of Paola Arlotta, Feng Zhang, and Aviv Regev at the Broad Institute and Harvard University. She applies a scalable genetic screening tool, in vivo Perturb-seq, to study the function of a panel of Autism-associated risk genes in the developing brain with single-cell resolution. Xin obtained her Ph.D. in neuroscience from The Rockefeller University, and her B.Sc in chemistry from MIT. She is the recipient of the Klingenstein-Simons Fellowship Award, G. Harold and Leila Y. Mathers Foundation Award, Donald E. and Delia B. Baxter Young Investigator Award, Larry L. Hillblom Foundation Award, Discovery Foundation Award from the California Institute for Regenerative Medicine, Early Career Investigator Award from the International Society of Autism Research, Allison Doupe Fellowship from the McKnight Endowment Fund, and was named as one of the ‘35 Innovators Under 35’ by MIT Tech Review in 2022.