Directing biosynthesis of bioactive triterpenes for pharmaceutical applications (OSBOURN_J18DTP)
The triterpenes are one of the largest and most diverse classes of plant natural products, with many useful biological properties. Some naturally occurring triterpenes have weak anti-inflammatory activity and are promising drug leads. Synthetic derivatives with improved activity have been generated but selective functionalisation of triterpene scaffolds using conventional chemistry is problematic, and the modifications made were limited. Phase three clinical trials of the best known of these synthetic triterpenes, bardoxolone methyl, were recently terminated because of side effects.
Recent advances in triterpene biosynthesis are now opening up new opportunities to systematically direct biosynthesis and modification of different triterpene scaffolds using enzymes, making it possible to understand for the first time the relationship between triterpene structure and function, and the features that determine potency and selectivity. This project exploits an innovative synthetic biology approach for quick and easy biosynthesis of novel triterpenes in a transient plant expression system. Triterpene analogs will be evaluated for anti-proliferative and anti-inflammatory activity, and the underlying signalling pathways and targets investigated. Structure activity relationship analysis will determine the specific moieties necessary for bioactivity and inform the further generation of structurally related compounds.
During this project the student will gain a solid foundation in plant biotechnology, molecular biology, synthetic biology, natural product chemistry, bioinformatics and enzymology. He/she will also become proficient in mammalian cell biology including cell culture using a variety of human cell types, bioactivity assays, biochemistry and immunology.
This project has been shortlisted for funding by the Norwich Biosciences Doctoral Training Partnership (NRPDTP). Shortlisted applicants will be interviewed as part of the studentship competition. Candidates will be interviewed on either the 9th, 10th or 11th January 2018.
The Norwich Biosciences Doctoral Training Partnership (NRPDTP) offers postgraduates the opportunity to undertake a 4 year research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three month professional internship (PIPS) during their study. The internship offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.
For further information and to apply, please visit our website: http://www.biodtp.norwichresearchpark.ac.uk
Full Studentships cover a stipend (RCUK rate: £14,553pa - 2017/8), research costs and tuition fees at UK/EU rate, and are available to UK and EU students who meet the UK residency requirements.
Students from EU countries who do not meet the UK residency requirements may be eligible for a fees-only award. Students in receipt of a fees-only award will be eligible for a maintenance stipend awarded by the NRPDTP Bioscience Doctoral Scholarships, which when combined will equal a full studentship. To be eligible students must meet the EU residency requirements. Details on eligibility for funding on the BBSRC website: http://www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf
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