PhD Studentship â Synthetic Organic Approaches for Covalent Inhibition of Protein-Protein Interactions (1046818EB)

PhD Supervisor: Dr Sam Thompson

Application Deadline: Rolling deadline; applications will be considered in order they are received.

Position available immediately

Studentship overview

We are looking for an enthusiastic and well-organized student with an interest in applying the full range of synthetic organic chemistry methods to design and construct conformationally well-defined molecules (foldamers) that covalently recognise key elements of protein surfaces. These scaffolds will form a toolkit of chemical probes for proteins that lie at the heart of intractable disease. Specific objectives of the project are: (i) the design, synthesis, and characterisation of new peptidomimetic scaffolds bearing covalent warheads; (ii) investigation of their ability to mediate the behaviour of therapeutically-relevant proteins; (iii) ‘catch and modify’ – chemical post-translational modification of amino acid side-chains.

Prior experience in Chemical Biology or Medicinal Chemistry is not required, but training in these areas will be provided for interested students during the PhD.

For recent relevant publications see:

Curr. Opin. Chem. Biol. 2018, 44, 30-38.

Chem Sci. 2016, 7, 6435-6439.

Angew. Chem. Int. Ed. 2015, 54, pp. 2649-2652.

Angew. Chem. Int. Ed. 2014, 53, pp. 3650-3653.

Background – structure and function in Nature

The inspiration and motivation for research in the group derives from the exquisite control that Nature exerts over structure and function – at both atomic and macromolecular levels. Unmet challenges in biology and medicine stem from gaps in our understanding of the basic science underlying these processes and a shortage of chemical tools for the interrogation and manipulation of specific interactions. Proteins constitute a bio-macromolecular class of particular interest due to their essential roles in all life forms, performing myriad structural, catalytic, and signalling functions. They are critically important in numerous disease states including cancer, diabetes, and neurodegeneration.

Organic synthesis as a key tool

Our major long-term goals are to develop a deeper understanding of the structure/function relationships governing therapeutically relevant protein-protein interactions (PPIs) and protein-misfolding conditions, and to develop molecular tools for their manipulation. In our group organic synthesis and methodology are central tools allied with rigorous structural and conformational assignment by solution- and solid-phase methods (especially NMR and X-ray). Combined with techniques from the fields of supramolecular chemistry, physical organic, and chemical biology this makes for multi-disciplinary projects. We have established collaborations with experts in molecular- and cellular-biology, providing insights into the behaviour of our chemical probes in physiologically relevant settings.

Research and training environment

The group is based in the modern synthetic chemistry laboratories in the School of Chemistry on the leafy Southampton Highfield Campus. Experimental chemistry is supported by world-class MS, NMR and X-ray facilities, with expert staff in each area to help design methods and analyze data. In addition to training in practical synthetic methods the student will be supported through regular group meetings and problem sessions. Opportunities to learn chemical biology and structural biology techniques will be provided through established collaborations. There will also be opportunities for the supervision of junior co-workers, and funds available for the presentation of work at national and international conferences.

Eligibility

The project is funded for 3 years and welcomes applicants from the UK and EU who have or expect to obtain a first or upper second class degree (or equivalent) in chemistry. Funding will cover full fees and a tax-free stipend at current research council rates of £ 14,777 per annum. 

Due to funding restrictions this position is only open to UK/EU applicants who meet the RCUK eligibility criteria

Application process

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 2018-2019 in the academic year field and click on the Research radio button.  Enter Chemistry in the search text field.

Please place Sam Thompson in the field for proposed supervisor.

If you are interested in the position and would like to find out more contact Dr Sam Thompson directly (st3a15@soton.ac.uk). Any queries on the application process should be made to fep-pgr-apply@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.

Closing Date: 31 Oct 2018
Post Type: PhD Studentship (Funded)