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Events
Towards precise editing of the microbiome within the gastrointestinal tract
Summary
Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. I will discuss our ongoing efforts to use CRISPR-Cas systems and bacteriophage to edit the microbiome within the mouse gut. We first established proof-of-concept with bacteriophage M13 and Escherichia coli. Extension to other gut bacterial species will require both novel genetic tools and the identification of suitable viruses for gene delivery. We identified and harnessed an endogenous type I-C CRISPR-Cas system in the disease-associated Actinobacterium Eggerthella lenta to confirm that a single gene is necessary for immune activation in the colon. We and others have isolated lytic bacteriophage targeting E. lenta; however, the bacterium evades phage targeting within the mouse gut. Taken together, these results provide initial support for the feasibility of microbiome editing in E. coli, while highlighting the numerous challenges ahead for generalizing these approaches to other human gut bacterial species of interest.
Speaker
Peter Turnbaugh, Ph.D., is a Professor in the Department of Microbiology & Immunology, the G.W. Hooper Research Foundation, and the Benioff Center for Microbiome Medicine at the University of California, San Francisco. He is also a CZ Biohub Investigator. For nearly two decades, his research has focused on the metabolic activities performed by the trillions of microbes that colonize our adult bodies. Dr. Turnbaugh and his research group use interdisciplinary approaches in preclinical models and human cohorts to study the mechanisms through which the gut microbiome influences nutrition and pharmacology. He received a B.A. in Biochemistry, Biophysics, and Molecular Biology from Whitman College and a Ph.D. in Microbial Genetics and Genomics from Washington University in Saint Louis. From 2010-2014 he was a Bauer Fellow in the FAS Center for Systems Biology at Harvard University, where he established an independent research group prior to starting his faculty position at the University of California, San Francisco. Notable honors include the Kipnis Award in Biomedical Sciences, the Needleman Pharmacology Prize, the Damon Runyon-Rachleff Innovation Award, the Searle Scholars Award, and the Burroughs Wellcome Fund Investigators in the Pathogenesis of Disease Award.