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A bioinformatics approach to understanding protein solubility tags


Department of Chemistry

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Dr J Warwicker , Dr R Curtis Applications accepted all year round Self-Funded PhD Students Only

About the Project

The crowded environment of a cell cytoplasm reveals that proteins and other biological molecules co-exist at high macromolecular concentrations. Many proteins, though, are difficult to express, purify, and/or store at the high individual component concentrations required for biotechnological applications. Several methodologies are used to counter this problem, including the use of solubility tag fusions, expression systems modified to aid protein folding, protein engineering, and the inclusion of additives for storage. Some of these methods make use of our current knowledge of relevant factors, such as facilitating native disulphide bond formation. However, this knowledge is limited. For example, fusion tags to enhance solubility can have quite different effects, depending on the protein of interest, in turn limiting the scope for accurate prediction of expression efficiency. This project seeks to improve our understanding of the role played by protein fusion solubility tags in expression. Importantly, some of the computational groundwork is in place, with a physico-chemical model for protein solubility being developed. Additionally, there exists a wealth of expression data in the literature. Since the effects of fusion tags are protein-dependent, it is anticipated that interactions between fusion tag and protein of interest could be critical to an improved understanding. These interactions will be the focus for developing the model for protein solubility. Both protein targets and solubility tags can be modelled, based on structure, and this information used to provide a predictive scheme for the differential effects of solubility tags.

Contact for further Information

Jim Warwicker
[Email Address Removed]
www.protein-sol.manchester.ac.uk
http://www.chemistry.manchester.ac.uk/study/postgraduate/researchdegrees/howtoapply/

Funding Notes

Applications are invited from self-funded students. For UK/EU tuition fees are £8,750 and International are £25,500 for 2019/20 academic year.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or the overseas equivalent) in a related area / subject. Candidates with an interest in biopharmaceuticals are encouraged to apply.

Please select PhD Biotechnology on the online application form.

References

Protein-Sol: A web tool for predicting protein solubility from sequence. Hebditch M, Carballo-Amador A, Charonis S, Curtis R and Warwicker J (2017) Bioinformatics 33:3098-3100.

Computational investigation of protein surface polarity and pH-dependence: application to antibodies shows that antibody-antigen interfaces tend to be relatively polar. Hebditch M and Warwicker J (2018) BioRxiv https://doi.org/10.1101/345231


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