Hybrid Seminar - Jonathan Weissman

Dr. Jonathan Weissman is pictured.
May 18, 2022 - 12:00pm
Location: 
601 Fairchild or Join Over Zoom
Investigator, Howard Hughes Medical Institute
Member and Landon T. Clay Professor of Biology, Whitehead Institute
Professor of Biology, MIT

Host: Graduate Students

Title: Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq

Abstract: A central goal of genetics is to define the relationships between genotypes and phenotypes. High-content phenotypic screens such as Perturb-seq (pooled CRISPR-based screens with single-cell RNA-sequencing readouts) enable massively parallel functional genomic mapping but, to date, have been used at limited scales. We have now performed genome-scale Perturb-seq targeting all expressed genes with CRISPR interference (CRISPRi) across >2.5 million human cells and present a framework to power biological discovery with the resulting genotype-phenotype map. We use transcriptional phenotypes to predict the function of poorly-characterized genes, uncovering new regulators of ribosome biogenesis (including CCDC86, ZNF236, and SPATA5L1), transcription (C7orf26), and mitochondrial respiration (TMEM242). In addition to assigning gene function, single-cell transcriptional phenotypes allow for in-depth dissection of complex cellular phenomena – from RNA processing to differentiation. We leverage this ability to systematically identify the genetic drivers and consequences of aneuploidy and to discover an unanticipated layer of stress-specific regulation of the mitochondrial genome. Our information-rich genotype-phenotype map reveals a multidimensional portrait of gene function and cellular behavior.

Please email [email protected] for a Zoom link to this seminar.

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