Hybrid Seminar - Jonathan Weissman

Dr. Jonathan Weissman is pictured.
May 18, 2022 - 12:00pm
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.

Business Office

Department of Biological Sciences
500 Fairchild Center
Mail Code 2401
Columbia University
1212 Amsterdam Avenue
New York, NY 10027

Academic Office

Department of Biological Sciences
600 Fairchild Center
Mail Code 2402
Columbia University
1212 Amsterdam Avenue
New York, NY 10027
[email protected]
212 854-4581