Mechanisms of Acquired Immunity in Bacteria

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Title: Mechanism of Acquired Immunity in BacteriaSenior personnel: Jennifer Doudna, University of California at Berkeley (Principle investigator)Scientific research: Control of viral infections in bacterial populations is critical to the use of microbes for a wide variety of applications including bioremediation and biofuel production. The discovery of RNA-based acquired immunity in bacteria, mediated by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs), provides an exciting opportunity to exploit natural pathways for regulating gene expression if the underlying molecular mechanisms can be discovered and manipulated. This project aims to determine how self versus non-self recognition is achieved, how new DNA sequences are acquired during viral infections and used to immunize cells against future infections. This project has the potential to transform the way we understand gene regulation in bacteria, and to reveal the molecular basis for a previously unknown and unanticipated mechanism of anti-viral defense. To understand the independent evolution and physiological functions of bacterial pathways utilizing RNA molecules to control genetic elements, it will be necessary to determine the molecular mechanisms of CRISPR activity. The potential impact of this project includes both discovering the mechanisms by which microbes acquire immunity to viruses, and providing the knowledge necessary to manipulate or engineer those systems for various applications. The project provides an exciting avenue of research for students, and is particularly appealing to undergraduates who are being exposed to protein and RNA biochemistry for the first time. There are ample opportunities for students to make truly new discoveries in this field, with potentially very high impact.Broader impacts: The primary investigator's lab has a successful history of training students at all levels in the creative dissection of molecular mechanisms involving RNA and RNA-protein complexes using a variety of experimental methods. The project will be conducted in a highly collaborative environment at UC Berkeley, which has become a de facto center for CRISPR research encompassing ongoing work in the laboratories of Jill Banfield, Phil Hugenholtz and Adam Arkin. An annual CRISPR conference attracts scientists from around the world to UC Berkeley to share their latest results. Students attend and present their work at this meeting, providing an outstanding opportunity for learning and discussing new results.