Supervisor: Prof. Matthew Powner
Application deadline: 5 pm on 18th February 2022
Start date: 26th September 2022
Applications are invited from suitably qualified candidates for a 4-year PhD Studentship. The Studentship is fully funded and available from September 2022. The successful candidate will be based in the Chemistry Department at UCL and supervised by Professor Matthew Powner.
The Powner group uses chemical synthesis and systems chemistry to explore the origins of life on Earth, whilst also developing novel, robust, green chemical reactions that can improve the synthetic and catalytic strategies available to access key biochemical targets. For example, amide and peptide bond formation is one of the most-important reactions in chemistry and in biology. Amide formation avoiding poor atom economy reagents was identified by the ACS Green Chemical Institute as the top challenge for organic chemistry, whilst effective peptide synthesis is an essential cornerstone of understanding the origins of life on Earth. To mutually address these challenges, we have developed a novel strategy for selective peptide synthesis. In 2019, we reported the facile, selective coupling of aminonitriles in water to make peptides (Canavelli et al. Nature 2019, 571, 546). Demonstrating the unique reactivity of aminonitriles could be coupled with biomimetic N-to-C terminal peptide synthesis. In 2020 we reported the first prebiotic synthesis of cysteine (Foden et al. Science 2020, 370, 865), then with cysteine in hand, we discovered Catalytic Peptide Ligation (CPL). Our novel peptide ligation exhibits outstanding chemo- and regio-selectivity for proteinogenic peptides, tolerating all twenty proteinogenic sidechain residues. CPL requires no activating agents – activation is built into the thermodynamically activated but kinetically stable nitrile substrate. CPL demonstrates robust, easy-to-synthesize, stable nitriles can replace difficult-to-synthesize, unstable thioesters in peptide ligation. A key goal of this project will be to build on CPL by developing a novel strategy to programme catalytic activation of both peptides and nucleic acids. This goal aims to advance our understanding of the origins of the central dogma of molecular biology, and develop a novel methodology for orthogonally controlled organocatalytic synthesis of peptides and nucleic acids in water.
This is an exciting opportunity for a student with a strong chemistry background to tackle one of the biggest problems in Science. The successful candidate will join a group of highly motivated scientists working to elucidate the chemistry that underpins the origins of life on Earth. Professor Powner is Professor of Organic Chemistry at UCL and an investigator of the Simons Foundation (New York, USA). International, multidisciplinary collaborative interactions within the on-going and extensive Simons Foundation Collaboration on the Origins of Life and the Leverhulme Trust Centre for Origins of Life in the Universe are anticipated.
The minimum requirement is a first class or upper second-class honours degree (MSci, MChem) or equivalent in Chemistry or closely related subject. Candidates must be highly self-motivated, and keen to work collaboratively in a team environment. Excellent experimental skills, a curiosity driven attitude to science, and good communication skills (both presentation and writing in English) are essential. UCL offers a world-leading scientific environment in the heart of London.
Applicants should send their applications (covering letter and CV including contact details for 2 referees) by email to Professor Matthew Powner at [Email Address Removed].
Suitable applicants will be required to complete MS Form entitled Application for Research: degree Chemistry programme. It is also essential that suitable applicants complete an electronic application form at http://www.ucl.ac.uk/prospective-students/graduate/apply (please select Research degree: Chemistry programme) and advise their referees to submit their references before the application deadline. All shortlisted applicants will be invited for the interview no more than 4 weeks after the application deadline.
Any admissions queries should be directed to Dr Jadranka Butorac and Holly Ambrose-Wilson at [Email Address Removed].