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Transcript
Background Metabolism shapes the cellular energy budget in response to physiological demands and changing environments, ultimately affecting many cellular functions. Cells use gene regulatory networks to coordinate and adapt the activity of multiple metabolic pathways. Understanding the interplay between complex regulatory networks and metabolism is key to uncover the mechanisms that control cellular adaptations, with applications such as the design self-adaptive pathways in Synthetic Biology or the identification of regulatory weak spots for future therapeutics. The successful candidates will join Dr Diego Oyarzún (Biomathematics, Imperial College London) in two exciting projects at the interface between Mathematics, Control Theory, and Systems/Synthetic Biology. The general aims of the projects are to develop mathematical tools to predict metabolic responses from gene regulatory networks and to showcase how new metabolic responses can be engineered in living cells. Both projects are part of a multidisciplinary partnership with Dr Fuzhong Zhang’s synthetic biology lab at the U Washington in St Louis. We seek someone open-minded, creative and willing to explore and learn new ideas as part of a multidisciplinary team. For inquiries, please email [email protected] with a CV. The start date for both posts is 01 September 2015. 1) Postdoctoral position on Systems and Synthetic Biology of metabolic adaptations We are looking for a postdoctoral researcher to investigate the analysis and design of genetic control circuits for bacterial metabolism. Our primary goal will be to build a theory that links the architecture and parameters of feedback regulation with the resulting metabolic phenotypes. The mathematical work requires a combination of nonlinear ODE analysis, biochemical modeling and parameter fitting. Through our collaboration with the Zhang lab, we will integrate theory and experiment to predict, measure and re-program the metabolic responses of E. coli to nutritional shocks. We will use the theory to devise genetic circuits that lead to new metabolic phenotypes and build them in the Zhang lab through architectural and parametric perturbations of E. coli's native regulation. We seek candidates with a PhD in a related area and a track record in Systems or Synthetic Biology, Control Theory for Biological Systems, or Mathematical Biology. The ideal candidate should have excellent theoretical and computational skills, a promising publication record in peer-reviewed journals, and the willingness or proven ability to collaborate with experimental scientists and handle biological datasets. The post is funded for 2.5 years and available to candidates from all nationalities. 2) PhD position on stochastic fluctuations in enzymatic reactions We are looking for a doctoral student to investigate the propagation of stochastic fluctuations between gene expression and metabolism. Although we know that many intracellular processes are inherently stochastic and cause significant cell-to-cell variability, stochasticity in metabolism is often overlooked on the basis that the large numbers of metabolites per cell average out stochastic effects. An increasing amount of theoretical and experimental evidence, however, suggests that fluctuations in enzyme expression have a key role in shaping metabolic phenotypes and growth. The primary goal of the project is to develop mathematical and computational tools to predict metabolic variability from gene regulatory networks. The project will rely on a combination of analysis and simulation of stochastic biochemical models; the ideal candidate should have excellent theoretical and computational skills, together with some knowledge of stochastic modeling/analysis of biochemical networks. Candidates should hold or be near completion of a Masters-level degree in a relevant area. Funding is available for 3 years to UK and EU nationals only.