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(BBSRC DTP) Solubilising Insoluble Proteins using Self-Assembling Supramolecular Structures


Project Description

Protein insolubility is a common problem for researchers working with isolated proteins that, due to hydrophobic patches on their surface, misfold and/or aggregate outside of their natural environment. The resulting insoluble materials are frequently hard (if not impossible) to characterise, and often do not display the useful and interesting properties researchers set out to explore. Methodologies that transform insoluble proteins into soluble species are therefore highly sought after as they may allow characterisation of novel proteins, or stabilise enzymes sufficiently for their catalytic function to be harnessed in abiological environments, for example in chemical manufacturing or bioremediation applications.

One rational approach to overcoming the solubility challenges associated with hydrophobic proteins is encapsulation of individual proteins within water-soluble capsules that have hydrophobic cavities. Such a ‘stealth coating’ will support the natural tendency of the protein to expose its hydrophobic residues on its surface while at the same time bringing the protein into solution enabling further study or application of the enzyme in aqueous environments. In recent years significant advances have been made in developing supramolecular structures with hydrophobic cavities that are able to accommodate a range of guest molecules including biomolecules.P1,2P We propose investigating the encapsulation of silicatein,P3P an industrially relevant enzyme with poor solubility, within self-assembling metal-organic materials. Following encapsulation the activity of the enzyme will be assessed and attempted characterisation of the structure, which has yet to be elucidated, will be undertaken.

The student appointed to this position will work on an exciting interdisciplinary project at the boundary of materials chemistry and biochemistry and will be fully trained in protein expression and purification techniques, chemical synthesis, NMR analysis, optical spectroscopy and PXRD as well as receiving high level training in mass spectrometry.

Riddell - https://imogenriddell.wixsite.com/riddellgroup
Wong - https://www.research.manchester.ac.uk/portal/l.s.wong.html
Barran - https://www.mbc.manchester.ac.uk/barrangroup/

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. K. Liang, R. Ricco, C. M. Doherty, M. J. Styles, S. Bell, N. Kirby, S. Mudie, D. Haylock, A. J. Hill, C. J. Doonan, P. Falcaro, Nat. Commun. 2015, 6, 7240;
2. D. Fujita, K. Suzuki, S. Sato, M. Yagi-Utsumi, Y. Yamaguchi, N. Mizuno, T. Kumasaka, M. Takata, M. Noda, S. Uchiyama, K. Kato, M. Fujita, Nat. Commun. 2012, 3, 1093.
3. S. Y. Tabatabei Dakhili, S. A. Caslin; A.S. Faponle, P. Quayle, S. P. de Visser, L. S. Wong, Proc. Natl Acad. Sci. USA 2017, 114 (27), E5285.

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