Chemical modification of proteins to probe Leishmania biology

Following the discovery that only 25,000 protein encoding genes exist in the human genome, it has become abundantly clear that the post-translational modification (PTM) of proteins must play a more significant role in generating the complexity of life than previously appreciated. The ability of chemists to characterise and harness the rich biological function of proteins both in vitro and in vivo is therefore becoming increasingly reliant on strategies to mimic such modifications site-specifically using chemical methods compatible with biological systems- a field known as bioorthogonal chemistry. In particular, the development of new bioorthogonal methods for protein modification has become essential to facilitate the evermore demanding modulation of function and utility required in chemical medicine, specifically by pharmaceutical companies with interests in the therapeutic applications of biologics. In this project we aim to redefine the bioorthogonal chemistry by establishing a new method for the chemical modification of proteins that generates a stable bonds under biologically relevant conditions and also enables multi-functionalisation. In this ambitious program, we will utilise existing expertise in chemical biology in combination with a range of interdisciplinary methods including chemical synthesis, organocatalysis, protein chemistry, unnatural amino acid mutagenesis and molecular biology to showcase the utility of these new bioconjugation reactions in collaborative ‘real world’ chemical biology studies and in the development of novel biomedical protein conjugates, including exploration of the structural and functional effects of N-terminal lipidation of immunogenic, Leishmania hydrophilic acylated surface proteins (HASPs).

All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills. All research students take the core training package which provides both a grounding in the skills required for their research, and transferable skills to enhance employability opportunities following graduation. Core training is progressive and takes place at appropriate points throughout a student’s higher degree programme, with the majority of training taking place in Year 1.

The candidate will receive interdisciplinary scientific training in synthetic chemistry, strategies for the chemical modification of proteins, protein purification, molecular biology and protein NMR

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. Shortlisted applicants will be invited for an interview to take place at the University of York on either the 13 or 15 February 2018. Candidates will be asked to give a short presentation prior to their interview by an academic panel.

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. This PhD project is available to study full-time or part-time (50%).