John Innes Centre – School of Chemistry (UEA)

Deadline: 29 November 2013. Available from 1 October 2014.　

Supervisor:
Professor Sarah O'Connor
Sarah.O'Connor@jic.ac.uk

The Project:

Natural products are biologically active molecules that, as their name suggests, are found in Nature. These compounds are used throughout the agricultural and pharmaceutical industries. Interestingly, modifying the natural product chemical structure often improves the biological activity. Halogenation- the installation of fluorine, chlorine or bromine atoms- of a natural product has been a particularly successful strategy to improve its biological properties. Unfortunately, chemical methodology used to halogenate small molecules is not environmentally friendly and often non-selective. The recent discovery of enzymes that carry out halogenation reactions (halogenases) provides a promising way forward to enzymatically produce halogenated compounds. However, to fully exploit halogenases we need to manipulate the substrate specificity of these enzymes to react with a wide variety of organic molecules.

In this studentship, the PhD candidate will examine the structure and sequences of halogenases. This information will be used to design mutations of the natural enzymes. The student will generate and then experimentally assay these mutants to assess for halogenase activity with new substrates. The student will also develop a high throughput colorimetric assay to facilitate screening of large numbers of mutants. The project will involve basic molecular biology, enzymology, protein modelling using standard software, as well as some basic organic chemistry. Ultimately, the student will generate halogenases with altered substrate and product specificity. These enzymes will be used in our on-going effort to reprogram complex alkaloid biosynthetic pathways to make new, valuable natural product-like molecules with biological activity.

Entry Requirements:

2:1 or 2:2 plus Masters. English Language – IELTS 6.5 overall with 6 in each category.

Funding:

Due to funding restrictions funding for PhD studentships from BBSRC is available to successful candidates who meet the UK Research Council eligibility criteria including the 3-year UK residency requirements. These requirements are detailed in the BBSRC eligibility guidelines:

http://www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf

In most cases UK and EU nationals who have been ordinarily resident in the UK for 3 years prior to the start of the course are eligible for a full-award. Other EU nationals may qualify for a fees only award. All candidates should check to confirm their eligibility for funding.

The current stipend for 2013/14 is £13,726 per annum.

Making Your Application:

For further information and to apply, please visit the 'How to Apply' page on our website by clicking Apply.

Additional Information:

In keeping with the postgraduate training policy of the Biotechnology and Biological Sciences Research Council (BBSRC) all students recruited onto this programme will be required to undertake a three months internship during the second or third year of their study. The internship will offer exciting and invaluable experience of work in an area outside of research, and full support and advice will be provided by a professional team from the UEA.

This project has been shortlisted for funding by the Norwich Biosciences Doctoral Training Partnership (DTP) – a collaboration between the Norwich Biosciences Institutes and the University of East Anglia. Shortlisted applicants will be interviewed as part of the Studentship Competition. The interview dates will be the 14th and 15th January 2014.

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