Structure and Function of BenM and CatM, Bacterial LysR-type Transcriptional Regulators

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LysR-Transcriptional Regulators (LTTRs) are the largest family of regulators in bacteria. They control diverse metabolic functions including amino acid biosynthesis, virulence, nitrate fixation, replication, and many other major processes. Despite their central role in allowing bacteria to respond to their environment, LTTRs are among the least studied types of regulators. The goal of this project is to expand our understanding of how these proteins function at an atomic level. Questions that will be addressed include: how do LTTRs bind to specific sequences of DNA in response to specific control molecules and what conformational changes take place when they bind their control molecules? New approaches to study LTTRs will be developed so that understanding these proteins and their potential beneficial applications can be advanced in the scientific community. The combined labs of the two PIs will focus on two proteins (BenM and CatM) from a soil bacterium, Acinetobacter baylyi. A wide range of methods will be used including mutant screens (genetics), DNA footprinting (molecular biology), and biochemical methods like tryptophan fluorescence, fluorescence polarization, and X-ray crystallography. The research will allow models to be developed to explain how diverse LTTRs function. Application of these studies may lead to novel biosensors and/or improved organisms for bioprocessing and bioremediation that can come from being able to modulate their functions. The research environment has a high educational impact. The project will allow high school, undergraduate and graduate students to have opportunities to experience experimental science and learn advanced methods in a highly collaborative environment that crosses multiple disciplines.