This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
Intellectual Merit: The majority of biological processes such as differentiation, growth, development and transformation are under tight control of cellular signaling systems. However, detailed mechanisms of how cells decide when and where to execute these processes remains one of the great mysteries of modern biology. Discovery of general principles underlying signal transduction in a simple unicellular organism is an essential step towards understanding the complexity of genetic and biochemical networks. Sensory behaviors of bacteria therefore serve as powerful models for exploring the molecular basis of cell signaling, differentiation and development. Sporulation in the soil bacterium Bacillus subtilis is one of the best studied model systems but the mechanisms of cell-fate decisions are still far from understood. The long-term goal of this project is to reveal how bacterial cells process signals to make cell decisions during sporulation. As a step toward that goal, this project aims to elucidate systemic properties of the phosphorelay sporulation initiating network with a synergistic combination of wet-lab experimentation, computational data analysis and mathematical modeling. The project also addresses fundamental biological questions on the relationship between population heterogeneity, noise, integrated system behavior, and decision making in response to environmental stimuli.
Broader Impacts: Project results are expected to unravel novel mechanisms by which environmental cues are measured and converted into dynamic changes in gene expression and subsequent differentiation. The uncovered mechanisms can be generally applicable to studies of complex developmental processes in a number of organisms. The model organism in this study is closely related to those causing food spoilage. Heterogeneity in sensitivity and resistance of spores, a well known obstacle of food preservation, may be ultimately related to variability in the execution of the sporulation program. The training of undergraduate and graduate students is an integral part of this project and the PIs are committed to working closely with trainees. The PIs will continue their efforts to recruit students from underrepresented minority groups into their labs through existing institutional programs. The project will provide abundant opportunities for the students involved in its experimental and/or mathematical modeling aspects to work together synergistically and therefore train scientists capable of effectively bridging the gaps between the biological sciences and quantitative disciplines.
