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Biology subjects

Clamons, S. E.

Publications and source records attributed to Clamons, S. E..

2 recordsLinked to original sources

Analysis of Circuits for Dosage Control in Microbial Populations

Designing genetic circuits to control the behaviors of microbial populations is an ongoing challenge in synthetic biology. Here we analyze circuits which implement dosage control by controlling levels of a global signal in a microbial population in face of varying cell density, growth rate, and environmental dilution. We utilize the Lux quorum sensing system to implement dosage control circuits, and we analyze the dynamics of circuits using both simplified analytical analysis and in silico simulations. We demonstrate that strong negative feedback through inhibiting LuxI synthase expression along with AiiA degradase activity results in circuits with fast response times and robustness to cell density and dilution rate. We find that degradase activity yields robustness to variations in population density for large population sizes, while negative feedback to synthase production decreases sensitivity to dilution rates.

synthetic biology↗

Modeling Dynamic Transcriptional Circuits with CRISPRi

Targeted transcriptional repression with catalytically inactive Cas9 (CRISPRi) promises to reproduce the functions of traditional synthetic transcriptional circuits, but with better orthogonality, programmability, and extensibility. However, CRISPRi lacks obvious cooperativity-a feature classically considered critical for several classic gene regulatory circuits. We use a simple dynamical model of CRISPRi to show that it can be used to build repressilators, toggle switches, and incoherent feed-forward loops. We also show that the function some of these circuits are expected to be sensitive to several key parameters, and we provide specifications for those parameters. Our modeling reveals key engineering requirements and considerations for the construction of dynamic CRISPRi circuits, and provides a roadmap for building those circuits.

synthetic biology↗