Download Background Metabolism shapes the cellular energy budget in

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.