This week on The Genetics Podcast, Patrick is joined by Xin Jin, Associate Professor in the Department of Neuroscience at The Scripps Research Institute. They discuss how in vivo Perturb-seq enables scalable and high-resolution modeling of neurogenetic disorders like autism, how introducing mutations directly into living mouse brains reveals cell-type vulnerabilities and convergent pathways, and why this approach could transform therapeutic development by identifying shared mechanisms across diverse genetic mutations.
Show Notes:
0:00 Intro to The Genetics Podcast
00:58 Welcome to Xin
01:52 Overview of in vivo Perturb-seq
05:10 Identifying de novo variants in autism spectrum disorder
09:00 Using perturbations to map how autism-linked mutations affect specific brain cell types
13:04 Applying Perturb-seq to other brain diseases
14:30 In vivo versus in vitro models and extending genetic screening approaches beyond the brain
18:44 Using in vivo models to trace variant effects, rank gene drivers, and uncover therapeutic pathways
22:35 Conservation of genes between mouse and human in the context of neurodevelopmental disease modeling
24:21 Impact of genetic discoveries on drug development by convergence onto common pathways
27:22 Xin’s early interest in science through her grandfather’s work in plant taxonomy and botany
29:48 Xin’s path from China to MIT and how early research shaped her scientific mindset
31:58 Reflections on AI’s rapid progress and limits in biology, and the need for new models
37:21 Closing remarks
Find out more
Jin lab (https://www.jin.scripps.edu/)
In vivo Perturb-seq explainer video (https://vimeo.com/549737357)
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