PhD Studentship in Chemical Biology and Drug Discovery

Location
United Kingdom
Posted
Aug 21, 2017
Closes
Nov 30, 2017
Organization Type
University and College
Hours
Full Time
PhD Studentship in Chemical Biology and Drug Discovery – Optimising the activity of a cyclic peptide protein-protein interaction inhibitor Chemistry

Location: 

Highfield Campus

 

Closing Date: 

Thursday 30 November 2017

 

Reference: 907617EB

PhD Supervisor: Ali Tavassoli

Application Deadline: rolling, appointment as soon as suitable candidate identified

 

Cyclic peptides are increasingly used in drug discovery against challenging targets such as protein-protein interactions. There are several advantages to the cyclic peptide scaffold, such as resistance to proteolysis and limited conformational freedom conferred by backbone cyclization, which yields molecules that engage their targets with high selectivity and affinity.1 The Tavassoli lab have pioneered several high-throughput screening platforms to generate and screen a genetically encoded cyclic peptide library of over a hundred million members against a variety of targets.2,3 We have previously demonstrated the optimization of cyclic peptides identified with this system into more drug-like molecules, and used them as chemical tools to inform decipher biological systems, as well as the starting point for drug development.4

We have been working with a major pharmaceutical company to identify a first in class inhibitor of a proprietary target. And the activity of the identified cyclic peptide has been verified in vitro and in cells. This project aims to identify the active motif of this cyclic peptide and use this information to develop more potent analogues. The project will be supervised by Professor Ali Tavassoli. The Tavassoli lab are an interdisciplinary lab, whose work spans synthetic chemistry, molecular biology and cell biology. The candidate will be provided with training and support in the techniques required for the project.

The ideal candidate will have a chemistry background and lab based experience of chemical biology or organic chemistry. The optimal candidate will be inquisitive and enjoy problem solving and working in an intellectually stimulating environment. The multidisciplinary nature of the project will provide outstanding training for the successful applicant. They will benefit from the existing expertise of the Tavassoli lab, receiving training in a wide variety of techniques and disciplines, and becoming expert in a range of experimental techniques, a skillset that will undoubtedly leave the students very well placed in terms of finding future positions.

The project is funded for 3 years and welcomes applicants from the UK who have or expect to have a first or upper second class degree in chemistry or related subjects. Funding will cover fees and a stipend at current research council rates of £ 14,553 per annum.

 

References

1. Tavassoli A., (2017) “SICLOPPS cyclic peptide libraries in drug discovery” Current Opinion in Chemical Biology, 38: 30-35.

2. Male A.L. et al.,(2017) “Targeting Bascillus anthracis toxicity with a genetically selected inhibitor of the PA/CMG2 protein-protein interaction” Scientific Reports, 7:3104.

3. Miranda E. et al., (2013) “A Cyclic Peptide Inhibitor of HIF-1 Heterodimerization That Inhibits Hypoxia Signaling in Cancer Cells.” Journal of the American Chemical Society, 135 (28): 10418-10425.

4. Asby D.J. et al., (2015) “Activation of AMPK via modulation of de novopurine biosynthesis with an inhibitor ofATIC homodimerization.” Chemistry and Biology, 22 (7): 838-848.

 

Due to funding restrictions this position is only open to UK applicants

Applications for a PhD in Chemistry should be submitted online at https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Search

Please ensure you select the academic session 2017-2018 in the academic year field and click on the Research radio button.  Enter Chemistry in the search text field.

Please place Prof Ali Tavassoli in the field for proposed supervisor/project.

General enquiries should be made ali1@soton.ac.uk. Any queries on the application process should be made to pgafnes@soton.ac.uk

Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified