Biology subjects

McBride, C. D.

Publications and source records attributed to McBride, C. D..

2 recordsLinked to original sources

bioRxiv2021

Predicting Composition of Genetic Circuits with Resource Competition: Demand and Sensitivity

The design of genetic circuits typically relies on characterization of constituent modules in isolation to predict the behavior of modules composition. However, it has been shown that the behavior of a genetic module changes when other modules are in the cell due to competition for shared resources. In order to engineer multi-module circuits that behave as intended, it is thus necessary to predict changes in the behavior of a genetic module when other modules load cellular resources. Here, we introduce two characteristics of circuit modules: the demand for cellular resources and the sensitivity to resource loading. When both are known for every genetic module in a circuit library, they can be used to predict any modules behavior upon addition of any other module to the cell. We develop an experimental approach to measure both characteristics for any circuit module using a resource sensor module. Using the measured resource demand and sensitivity for each module in a library, the outputs of the modules can be accurately predicted when they are inserted in the cell in arbitrary combinations. These resource competition characteristics may be used to inform the design of genetic circuits that perform as predicted despite resource competition.

synthetic biology↗

bioRxiv2020

Trade-offs in Robustness to Perturbations of Bacterial Population Controllers

Synthetic biology applications have the potential to have lasting impact; however, there is considerable difficulty in scaling up engineered genetic circuits. One of the current hurdles is resource sharing, where different circuit components become implicitly coupled through the host cells pool of resources, which may destroy circuit function. One potential solution around this problem is to distribute genetic circuit components across multiple cell strains and control the cell population size using a population controller. In these situations, perturbations in the availability of cellular resources, such as due to resource sharing, will affect the performance of the population controller. In this work, we model a genetic population controller implemented by a genetic circuit while considering perturbations in the availability of cellular resources. We analyze how these intracellular perturbations and extracellular disturbances to cell growth affect cell population size. We find that it is not possible to tune the population controllers gain such that the population density is robust to both extracellular disturbances and perturbations to the pool of available resources.

systems biology↗