A bioinformatics approach to understanding protein solubility tags

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

School of Chemistry, University of Manchester

About This PhD Project

Project Description
Funding Notes
Email Now
References

Project Description

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 protected]
http://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 £8,500 and International are £24,500 for 2018/19 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

Related Subjects

Email Now

Recipient *

Your first name *

Your last name *

Your telephone number

Your e-mail address *

Your CV (2MB limit)

Where are you currently living? *

Your nationality *

Your message * (please edit as appropriate)

Insert previous message below for editing?

You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here

* required field

Send a copy to me for my own records.

Your enquiry has been emailed successfully

View all PhDs at University of Manchester

Find out about studying in United Kingdom

Related PhDs

Our Sites

Main Menu

Postgrad LIVE! Study Fairs

A bioinformatics approach to understanding protein solubility tags

University of Manchester

School of Chemistry

Manchester