The reliable production of protein-based drugs and therapeutics requires complete understanding of the steps in their synthesis, from gene expression to the activity of the final folded and purified protein. One solution to create a simplified production route is to accumulate the recombinant proteins as insoluble inclusion bodies (IBs), which can both accumulate to very high levels inside the producing cell and be easily extracted, while retaining activity. In a collaboration between the Universities of York and Teesside, with biologics manufacturer FujiFilm Diosynth Biotechnologies (FDBK) based on Teesside, we have developed several model proteins to investigate how the producing cell, the bacterium Escherichia coli, responds to the accumulation of these IBs, compared to soluble versions of very similar proteins.
The student will use a broad range of molecular, biochemical and computational techniques to understand the fundamental cellular responses of E. coli to IB formation. In our matched sets of closely related IB and non-IB producing proteins, the student will use molecular biology tools to create hybrid proteins to understand the relationship between protein structure and IB formation and will undertake industry-like fermentations at FDBK Billingham during the project. Matched transcriptomics data is available which will be complemented with proteomics data. Importantly the student will use and help develop our new data integration tool called MORF for the omics data entry and analysis (https://morf-db.org/) and ideally will have some coding experience in Python. The student will then generate hypotheses about host factors involved in IB formation and investigate their effect using our model proteins and other known IB-forming proteins available through FDBK. The student will work primarily in York but will spend time at Teesside and will also do placements at FDBK as an integral part of this academic/industry partnership. Further training is also provided by IBioIC.
The Department of Biology at the University of York is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.
Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions.
Programme: PhD in Biology (4 years)
Start date: 1st October 2021
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