Signal sensing is essential for bacteria that live in fluctuating environments. However, even a group of isogenic bacteria, subject to identical culture conditions, often exhibit heterogeneity in phenotypes. This multi-stability can be explained by stochastic transitioning among multiple stable states of gene expression which are often the results of positive feedback loops in gene regulatory networks. Our overarching goal is to determine the governing design principles of biological robustness by building complex genetic circuits from the bottom-up. To this end, we have constructed genetic sensors that respond to environmental signals (e.g., pH and light) and bistable switches that can generate noise-tolerant responses to fluctuating environmental inputs. These switches are based on the sequestering interaction between a transcription factor (an activator) and an anti-activator, along with multiple positive feedback loops (1). Importantly, these switches are functional over a wide range of parameters and endow the cells with a long-lasting memory. We are assembling modular sensors, logic gates, and memory devices to construct robust, programmable probiotic strains that would reproduce in the intestine where parasite eggs are produced, and would come out of the human body with the parasite eggs and kill them. We will present progress towards development of such engineered microbes, which can be programmed to kill parasite eggs only when user-defined conditions are met.<br/> <br/>(1) T Shopera, WR Henson, A Ng, YJ Lee, K Ng and TS Moon. Robust, tunable genetic memory from protein sequestration combined with positive feedback. <i>Nucleic Acids Res.</i> DOI: 10.1093/nar/gkv936 (2015)

Construction of robust, tunable genetic circuits to prevent infectious diseases

251st National Meeting (2016)

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