Background: Cyanobacteria are the simplest and most genetically-tractable organisms capable of oxygenic photosynthesis, the biochemical process which generates the energy and oxygen that support life on Earth. As well as being excellent model organisms for studying the fundamentals of oxygenic photosynthesis, cyanobacteria have great potential as whole-cell biocatalysts for green biotechnology, using sunlight and atmospheric carbon dioxide to support the synthesis of products of interest. Cyanobacteria are also ideal testbeds for re-imagining the photosynthetic light-reactions to enhance the overall efficiency of photosynthesis in plants for improved crop-production.
The synthetic biology toolbox for cyanobacteria has expanded rapidly in the last few years [1] but production using cyanobacteria is not yet commercially viable, partly because it is difficult to rationally design productive and genetically stable metabolic pathways. However, modern DNA assembly allows construction of large libraries (>1,000,000) of many pathway-encoding construct variants. Using such strategies to vary the expression of each enzyme combinatorially, coupled with complementary high-throughput enzyme evolution approaches, allows high-performing variants to be identified by screening for the desired product/trait.
The project: This interdisciplinary PhD project will use synthetic biology platforms for combinatorial construction of metabolic pathway constructs and high-throughput enzyme evolution developed by the Heap lab [e.g., 2, 3] to engineer productive and genetically stable biosynthesis pathways in cyanobacteria, as well as in anoxygenic phototrophic bacteria [4] and model heterotrophs like Escherichia coli [5]. The student will receive broad and comprehensive training in molecular biology and genetic engineering techniques, analytical methods such as HPLC and LC/MS, protein biochemistry, protein engineering, de novo protein design and structural biology.
Supervision: This interdisciplinary project will be jointly supervised by a supervisory team with combined expertise in molecular photosynthesis, microbial photo-physiology, synthetic biology, and metabolic engineering. The student will be based in the Hitchcock lab in the Department of Molecular Biology and Biotechnology at the University of Sheffield and will also visit and work closely with the group of Dr John Heap ([Email Address Removed]) in the School of Life Sciences at the University of Nottingham. The third co-supervisor, Professor Neil Hunter FRS ([Email Address Removed]), is head of the Molecular Photosynthesis Research cluster in Sheffield, a diverse set of researchers which the successful applicant will join. Please contact Dr Andrew Hitchcock ([Email Address Removed]) for informal enquiries.
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