Center for Computational Biology Seminar: Combining DNA Synthesis, Multiplexed Reporters, and Genome Engineering to better Understand Human Gene Regulation and Protein Function

Seminar: Biosystems and Computational Biology: EE: CS | September 4 | 4-5 p.m. | 125 Li Ka Shing Center

 Sriram Kosuri, Assistant Professor, UCLA

 Center for Computational Biology

Sri Kosuri is an alumnus of UC Berkeley (BS, Bioengineering '01; Go Bears) and an Associate Professor in the Department of Chemistry and Biochemistry at UCLA, with appointments in the Institute for Quantitative and Computational Biology, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, Broad Stem Cell Center, and the Jonsson Comprehensive Cancer Center. The Kosuri laboratory focuses on developing multiplexed methods to explore relationships between DNA sequence and genetic function at very large scales in bacteria, yeast, and mammalian cell lines. In recent years, the lab has explored questions in synthetic biology, population genetics, evolutionary biology, functional genomics, neuroscience, and drug development. Dr. Kosuri is currently on leave working at a new drug discovery startup located in Berkeley called Octant.

His laboratory develops new methods that link a genetic function such as transcription, splicing, or signal transduction, to genetically-encoded barcoded reporters that can be identified and measured by next-generation sequencing. This allows them to molecularly multiplex hundreds to thousands of such experiments in a single flask, and to use large-scale DNA synthesis as a way to explore these sequence-function relationships. In this talk, he will discuss two of his lab's recent efforts in bringing these practices to problems in human biology. In the first, we explore how extant human genetic variation affects the process of exon recognition during pre-mRNA splicing using a new multiplexed assay in human cell lines. We find a surprisingly large number of rare genetic variants lead to large-effect loss of exon recognition. In the second, we develop a new reporter for G-protein coupled receptor signal transduction. We use this system to characterize signal transduction for all possible single amino acid mutations to the beta-2-adrenergic receptor and uncover novel motifs required for signal transduction, as well as use the system to do large-scale de-orphanization efforts on mammalian olfactory receptors.

 All Audiences

 All Audiences

 Light refreshments will be provided at reception from 3:30 - 4:00pm, 125 LKS foyer.