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(BBSRC DTP) Understanding and Harnessing Enzymes for Organosilicon Chemistry


Department of Chemistry

Manchester United Kingdom Biochemistry Biophysics Computational Chemistry Molecular Biology Organic Chemistry Pharmaceutical Chemistry Synthetic Chemistry

About the Project

In synthetic chemistry, there has been increasing prominence in the use of engineered enzymes to execute chemical transformations for the biosynthesis of drugs and fine chemicals. These biocatalysts are attractive since they offer highly efficient synthesis in terms of yields and selectivity; together with an inherent environmental sustainability. However, one area where biocatalysis has been relatively unexplored is in silicon-containing (organosilicon) chemistry.
Marine sponges that use silicon (in the form of silica) as part of their inorganic skeleton utilise enzymes to polymerise silicic acid (H4SiO4) into silica. These enzymes, termed the silicateins, are uniquely interesting as they catalyse a reaction that is rare in living systems, the formation of Si-O bonds. Crucially, we have recently shown that these enzymes accept organic silanes, alluding to the possibility of utilising these proteins for a wider range of organic chemistry. Harnessing the ability to form (and hydrolyse) these bonds from their corresponding silanol and alcohol with a high level of control would be both eco-friendly, economically valuable and enable a new range of synthetic reactions.
The successful candidate will undertake a comprehensive research and training programme in biocatalysis, which will include components of (i) investigating the enzymes’ mechanism of catalysis using a range of analytical methods such as fast (femtosecond to second) spectroscopy, X-ray crystallography; as well as molecular dynamics simulations and density functional theory modelling; (ii) develop new engineered enzymes, and apply these to novel synthetic reactions for the production of complex small molecules and materials precursors.
This project will suit a candidate with an interest in biological chemistry, with a background in synthetic chemistry, biochemistry or a related field. The candidate will primarily be based at the Manchester Institute of Biotechnology (www.mib.ac.uk), the UK’s first purpose built institute for interdisciplinary research at the interface of the physical and life sciences. The institute has state-of-the-art laboratories for both synthetic chemistry and molecular biology, as well as the facilities for advanced molecular characterisation and analysis. Furthermore, the researchers will also have access to all the shared facilities available in the School of Chemistry, one of the largest and best equipped in the UK.

https://www.research.manchester.ac.uk/portal/l.s.wong.html
https://www.youtube.com/watch?v=XOXJ8fpg3Wk (Video overview of the research area)

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

MIB

Funding Notes

Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

[1] S. Y. Tabatabaei Dakhili, S. A. Caslin, A. S. Faponle, P. Quayle, S. P. de Visser, L. S. Wong, Proc. Natl. Acad. Sci. 2017, 114, E5285-E5291. http://dx.doi.org/10.1073/pnas.1613320114
[2] R. L. Brutchey, D. E. Morse, Chem. Rev. 2008, 108, 4915-4934. http://dx.doi.org/10.1021/cr078256b

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