This CAREER award from the Chemistry of Life Processes Program in the Division of Chemistry will support the work of Dr. Emily Weinert at Emory University to determine the mechanism of signal transduction and the role of globin-coupled sensor signaling in diverse bacteria. Bacteria form three-dimensional communities, termed biofilms, in response to environmental signals, which protect the bacteria from predation and environmental stress. To understand how bacteria sense and respond to their environment, a detailed knowledge of the environmental signals, proteins, and pathways that affect bacterial growth, metabolism, and biofilm formation is required. The results from the proposed research will elucidate the role of oxygen concentration in controlling bacterial phenotypes, determine the molecular mechanism of oxygen sensing, and potentially highlight novel methods to alter oxygen-dependent signaling. The broader impacts emanate from teacher-scholar activities, which are integrated into the research plan. These activities will pique student interest in the scientific process and encourage students to pursue and remain in careers within the sciences. Proposed activities include 1) mentoring of high school, undergraduate, and graduate students, 2) development of an undergraduate chemical biology class to introduce students to the primary literature and grant writing, and 3) establishment of two new organizations at Emory, a graduate chapter of Advancing Women in Science and an undergraduate Chemistry research honor society.
This research project is centered on determining the mechanism of signal transduction and the role of globin-coupled sensor signaling in diverse bacteria. Globin-coupled sensors (GCS) are heme-containing signaling proteins proposed to serve as oxygen sensors in vivo. A number of GCSs are predicted to contain diguanylate cyclase domains, which catalyze production of c-di-GMP, a bacterial second messenger that regulates biofilm formation. To understand complex, heterogeneous biofilms found in the environment, the factors regulating biofilm formation, such as gaseous environment, must be understood at both the molecular and organismal level. Although putative oxygen-sensing GCSs have been identified in the genomes of many bacteria, the mechanism of signal transduction within the protein, the role of the middle domain, and the downstream effects of oxygen signaling are poorly understood. Therefore, understanding the mechanisms by which bacteria sense oxygen levels will help to illuminate how bacteria respond to changing environmental conditions and potentially allow for reengineering of these pathways. The aims of this research proposal are to 1) investigate the ligand-dependent activity of GCSs with varying middle domain lengths from diverse bacteria, 2) identify the mechanism of signal transduction and role of the middle domain, and 3) characterize interacting partners and downstream phenotypes controlled by GCS signaling in vivo. By understanding the effect of varying oxygen levels on bacterial phenotypes at the molecular level, it will be possible to elucidate the role of GCSs in oxygen-dependent biofilm formation and metabolic changes in a wide variety of organisms.
This project is co-funded by the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences
