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Improving biotherapeutic production through experimental evolution & genomics

Project Description

Bacteria are often used as industrial workhorses in various biotechnological applications to produce protein biotherapeutics. These production systems are often based on plasmid vector technology, such as pAVEway vector system used by FujiFilm Diosynth Biotechnologies (FDB), that allow production of multiple different proteins in one bacterial background (Escherichia coli). However, carrying and expressing such plasmids is often costly to the bacterium, which can considerably constrain the process efficiency due to metabolic burdens. While it has been shown that these costs can be alleviated via compensatory mutations, the molecular mechanisms underlying plasmid fitness costs remain poorly understood.

To achieve this the student will use an interdisciplinary bioengineering approach to combine experimental evolution, genome sequencing and genetic engineering to create novel E. coli genotypes with improved function in batch fermentation. The main objectives are to use experimental evolution to select for E. coli genotypes that exert reduced cost of plasmid carriage; to employ full genome sequencing to identify genetic factors that influencing plasmid carriage and to improve process efficiency by engineering novel E. coli genotypes for improved biotherapeutic production.

The student will have a fantastic opportunity to work across two labs that are experts in E. coli and experimental evolution using a range of molecular microbiology, genetic and genomic methods. The student will spend at least 3 months working in the industry partner FDB (based on Teesside) to test evolved and engineered strains for improved biotherapeutic production. The student will join a vibrant community of researchers working in industrial biotechnology both at York and within FDB as part of their Centre of Excellence in Bioprocessing 2.0. An ideal candidate will have a background including interests in microbiology and molecular molecular or evolutionary biology and genetics, with a general interest in their application for biotechnology.

Funding Notes

Funding: This is a 4-year studentship fully-funded by FujiFilm Diosynth Biotechnologies (FDB). The studentship covers: (i) a tax-free stipend at the standard Research Council rate (around £15,000 per year), (ii) tuition fees at UK/EU rate, (iii) research consumables and training necessary for the project.

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

Research output data provided by the Research Excellence Framework (REF)

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