This project is a theoretical investigation focused on the phenomenon of competence in Bacillus subtilis. Competence is the state during which this bacterium can accept and incorporate, into its own genome, DNA from the environment. The competent state is adopted at random times and for random durations and is thought to be an evolutionary strategy to facilitate adaptation to changing environmental stress. In this project computational and simulation approaches will be used 1) to develop hypotheses for plausible theoretical gene regulation topologies that underlie competence, and 2) to compute, numerically, their observable phenotypes. The approach consists of systematically simulating the stochastic behavior of the hypothetical gene regulatory circuit topologies. The work includes deriving, analytically, the continuous limit of each model; it involves connecting the discrete and continuous models, and performing phase plane analyses. Parameter continuation will be used to map the dynamical regimes of these systems. Comparisons with the stochastic behavior will be made and differences leading to potentially interesting biological phenotypes will be identified. The project is expected to suggest new gene regulation circuits to "reengineer" in the bacterium and test in the laboratory. Key issues that are addressed in this project concern the redistribution of noise in gene regulatory networks as a function of circuit topology; whether general principles of noise conservation (or trade off) exist; and the extent to which such principles might inform our understanding of evolutionary processes.
Broader Impacts: This project will provide training at the interface of mathematics, computer simulation and biology for undergraduate and graduate students, and for a postdoctoral fellow who is interested in using mathematics and computational simulations in the study of biology. The STARS program (Science Teacher Access to Resources at Southwestern) will provide opportunities for high-school teachers and their students to become engaged in this project. New educational programs at the interface of mathematics and biology will be developed, together with new portable simulation-oriented teaching material for direct use in the classroom. STARS will facilitate interactions with the Dallas Independent School District (DISD) schools and provide access to this project for traditionally underrepresented groups.
