EASTBIO DTP PhD studentship: "Value-added natural product derivatives by rational semi-synthesis"

EASTBIO - the BBSRC East of Scotland Bioscience Doctoral Training Partnership - is a partnership between the Universities of Aberdeen, Dundee, Edinburgh and St Andrews; the Scottish Universities Life Sciences Alliance (SULSA); and the Scottish Universities Physics Alliance (SUPA). A fully funded 4-year EASTBIO PhD studentship (fees and stipend at the standard rate) is available from September 2014 for candidates with a strong academic record and that satisfy BBSRC studentship eligibility requirements (see http://www.eastscotbiodtp.ac.uk/how-apply if you are unsure).
The ability of living organisms to biosynthesize complex bioactive organic molecules efficiently from cheap and ubiquitous resources is unmatched by synthetic chemistry. However although over 200,000 natural products have been reported to date, only 5-15% of these substances have ever been the focus of phytochemical or pharmacological investigations. In addition, derivatization of natural products using synthetic chemistry is often necessary to achieve desirable properties, as evidenced by industrial semisyntheses of the chemotherapy drugs docetaxel or ixabepilone. New approaches are needed to efficiently harness the diversity of natural products for the production of novel high-value chemicals.
In this project you will use in-silico rational drug design methods to identify putative biomolecular targets of a given natural product and to screen natural product libraries against given drug targets. You will prepare natural products using fermentation techniques. You will use molecular modelling methods to identify strategic modifications of natural-product cores that will improve bioactivity and ADME properties. You will devise new ways to derivatize the natural products with synthetic organic methodologies. Biological testing of the natural products derivatives will be performed in collaboration with other research groups at Edinburgh and elsewhere. Initial efforts will focus for instance on derivatives of the antibiotic anisomycin as putative antiproliferative agents, and the identification of novel natural product derivatives that bind cyclophilins as putative antiviral agents.
The overall goal of the project is therefore to combine the techniques of biosynthesis, molecular modelling, and organic synthesis into a new technology platform for efficiently adding-value to biogenic substances. A 3 month professional internship will augment the scientific training provided by this project. The broad set of skills that will be acquired through the project will provide outstanding preparation for the student for a future career in the field of biotechnology, in either an academic or industrial setting.