Model-based design for synthetic (micro)biology

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My research program involves the development and analysis of computer models of cellular biology, to aid in investigations of cellular behaviours and for prediction of the effects of interventions. The proposed research involves applying this modelling approach to the biology of microbes. These unseen organisms have impact on major aspects of human activity, from food production to health, from the environment to manufacturing. We will use computer models to improve our understanding of the behaviour of individual microbial cells and of microbial populations, with the goal of enabling manipulation of microbes to benefit humanity. We propose research activities targeted toward three short-term aims:******Our first aim is to investigate strategies for manipulation of microbial populations in the environment by delivery of genetic elements that alter their behaviour. We are motivated by the possibility of suppressing populations of antibiotic resistant bacteria, either by rendering them antibiotic-susceptible, or by killing them outright. We will investigate the performance of a number of such manipulation strategies in laboratory populations, and will build computer models to consolidate our understanding of their behaviour and to provide predictions of performance in potential applications.******Our second aim is to develop computer models of interacting microbial populations. In most natural environments, microbes occur in ecologies consisting of large numbers of interacting species. The research community has only recently begun to understand the complexities of these assemblies. We have acquired video microscopy of simple two-species communities in the lab. By developing computer models of these interacting populations, we will be taking an important first step toward generating mechanistic descriptions of natural microbial ecologies. These descriptions will allow us to predict the effect of intervention in these systems toward improvements in health, agriculture, and the environment.******Our third aim takes advantage of light-sensing systems from photosynthetic microbes. These can be ‘re-wired' to allow control by light of a range of cellular activities. This ‘optogenetic' system allows unprecedented control of cellular activity by time-varying light inputs. We have built a computer-controlled light excitation system with which we can explore this system. Using a computer model, we will identify light inputs that provide maximum informativeness for probing cellular behaviours. We will then investigate the use of this system for temporal control in metabolic engineering, with the goal of improving efficiency in biomanufacturing of drugs and other useful chemicals. ******This work will result in improvements in our ability to manipulate microbes to our advantage, contributing to solving a range of pressing problems in health, agriculture, manufacturing, and the environment.