Switchable orthogonal gene control systems for metabolic engineering and improving production of biotechnological products

The University of Nottingham has a strong track record in microbial synthetic biology. It has been awarded research funding of over £14M by BBSRC and EPSRC in 2014 to further strengthen this area, to develop technologies and carry out applied and fundamental research on anaerobic and aerobic bacteria utilising waste gases including CH4, CO, CO2 and H2. A core aim of the new Synthetic Biology Research Centre (SBRC) is to generate new knowledge in a coherent, multi-disciplinary environment that ultimately leads to optimisation of production processes to sustainably generate fine chemicals or biofuels from microbial systems.

The SBRC’s ambition is to create optimised chassis for sustainable industrial production of carbon-based chemicals to replace petrochemical derived commodity compounds, utilise waste GHG, alleviate climate change and facilitate wealth creation through the waste economy.

We seek a talented graduate with a keen interest in synthetic biology to study for a PhD in the following topic area:
Rapidly developing synthetic biology tools and applications play increasingly important role within the context of metabolic engineering of microbial organisms for production high value chemicals and various precursors for biotechnological products and pharmaceuticals. Tuneable and switchable systems with reversible induction or repression of metabolic genes at any required time, reducing undesirable effects caused by over- or under-production of metabolic enzymes are vitally important. A fast-responding to external stimuli and with good level of a signal-to-noise ratio control systems are an essential tool for regulating metabolic pathways in complex biological systems. Efficient control of biological systems will guide to maximising production of the desired products by increasing flux and bypassing the problem of unwanted metabolic load. The rhamnose, arabinose, propionate, anhydrotetracycline and other chemical-based inducible and repressible promoter systems are commonly used for gene expression control in bacteria.

The project aims to develop a platform for switchable gene expression control systems that will effectively allow either to fine tune gene expression in rationally designed metabolic pathways increasing efficiency of production in biotechnologically important microorganisms or to switch-off completely production of those enzymes, which are no longer required increasing metabolic flux towards desired chemical or other biotechnological product. The project will involve several multidisciplinary components for designing and engineering of gene control mechanisms in metabolically versatile bacteria with a high biotechnological potential such as Ralstonia eutropha.

The successful candidate will join a highly motivated and well-funded team of research scientists dedicated to the exploitation of industrial important microorganisms. The SBRC is located in state-of-the-art facilities in the recently completed, £25M Centre for Biomolecular Sciences (http://www.nottingham.ac.uk/cbs), a multidisciplinary research environment. This will provide opportunity to train in microbiology, analytical biochemistry and wide spectrum of synthetic biology approaches.