EP 199: Functional genomics at scale: Using in vivo perturbations to study genetic risk variants in the brain with Xin Jin of Scripps Research Institute

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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