PhD Studentship: Directing biosynthesis of bioactive triterpenes for pharmaceutical applications (OSBOURN_J17DTP)

University of East Anglia - School of Biological Sciences

Start Date: 1st October 2017

Supervisor: Prof. Anne Osbourn

Project description:

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/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. 

Person specification: Minimum entry 2:1

Funding notes: Full Studentships cover a stipend (RCUK rate: £14,296 pa – 2016/7), 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:

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South East England