A bioinformatics approach to understanding protein solubility tags

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 [1-3]. 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.

Qualification
Applicants should have or expect a good II(i) honours degree (or an equivalent degree) in a Biosciences, Computational Biology, Chemical or Chemical Engineering area.

Contact for further Information
Please contact Dr Jim Warwicker (Email - [Email Address Removed]) for further information. Applicants should provide details of their qualifications, including a CV and a personal statement. A formal application must be submitted to be considered.