CAREER: Probabilistic Decision-Making in Natural and Synthetic Gene Circuits

California Institute Of Technology, Pasadena CA

Investigators

Abstract

In response to stress, some organisms effectively 'roll the dice,' selecting randomly from among various possible genetic programs. For example, in the bacteria Bacillus subtilis, individual cells respond to nutrient limitation differently: some become competent to take up DNA from the environment, others differentiate into a robust spore, while the rest continue to grow and divide. This ability to make random choices is crucial in microbial survival, and used throughout the development of multicellular organisms. The Elowitz lab will address the question of how genetic circuits allow otherwise identical cells to choose their fate randomly, using the soil bacteria Bacillus subtilis as a model system. The well-characterized genetic circuitry underlying the decision to sporulate will be analyzed using two complementary approaches. First, automated time-lapse fluorescence microscopy, together with quantitative image analysis, will be used to determine detailed gene expression dynamics in individual cells during the decision-making process. Second, synthetic biology techniques will be used to design, construct, and analyze simpler genetic circuits in Escherichia coli that generate similar responses. These synthetic circuits function as in vivo models of the more complex natural circuits they emulate. Mathematical modeling will inform all aspects of the research program, both in the analysis of data and formulation of hypotheses. The Broader Impact of the research will include the development of new curricula in systems biology and synthetic biology and the generation of tools for the research community, including software for single-cell analysis of time-lapse movies of bacterial growth.