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Inhibitors and probes for carbohydrate-active enzymes

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The field of chemical biology aims to design and synthesize chemical tools (such as inhibitors, substrate mimics, or enzyme probes) to answer fundamental questions in biology. In our group we use cutting-edge chemical biology approaches to advance our knowledge of some of the key enzymes responsible for synthesizing specific carbohydrate structures in cells. Carbohydrates play many roles in cells from all kingdoms of life. In addition to their well-known role as an energy source, they also have important functions in, for example, communication between cells, cell-pathogen interactions, intracellular signalling, and maintaining a stable cellular environment. The various sugar building blocks are often linked together to create very complex and diverse structures and can be linked to other biomolecules such as proteins, a modification referred to glycosylation. These diverse structures are formed by the consecutive actions of networks of cellular enzymes, which together dictate the levels and structures of carbohydrates presented on the cell surface. Due to their importance in cell recognition and signalling, defects in the functioning of one of these enzymes often leads to disease. There is a clear need for novel tools that can help us better understand the molecular mechanism of individual enzymes and their roles in normal functioning of the cell as well as in pathological processes.

The specific form of glycosylation that our group is interested in is O-mannosylation, the modification of cell-surface proteins with a glycan in which the first sugar, linked to protein hydroxyl groups, is a mannose residue. In this project, we will focus on a set of enzymes responsible for the biosynthesis of O-mannosylated proteins. We will develop inhibitors for these enzymes as tools to study their molecular mechanism and role in the O-mannosylation pathway. Identified hits will then be used to develop covalent probes that enable analysis of the enzyme’s cellular location, turnover, and activity in a variety of conditions. The range of techniques used includes organic synthesis, mammalian cell culture, and mass spectrometric analysis.

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. In conjunction with the Core training, students, in consultation with their supervisor(s), select training related to the area of their research.

The training program will be of a cross-disciplinary nature, providing training in organic and analytical chemistry and a basic understanding of cell biology. Specific techniques include organic synthesis, HPLC purification, LC-MS and NMR characterization, mammalian cell culture, SDS-PAGE, immunoblotting, and affinity purification.

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel. Chemistry at York was the first academic department in the UK to receive the Athena SWAN Gold award, first attained in 2007 and then renewed in October 2010 and in April 2015.

Funding Notes

This project is open to students who can fund their own studies or who have been awarded a scholarship separate from this project. The Chemistry Department at York is pleased to offer Wild Fund Scholarships to those from countries outside the UK. Wild Fund Scholarships offer up to full tuition fees for those from countries from outside the European Union. EU students may also be offered £6,000 per year towards living costs. For further information see: View Website

Related Subjects

How good is research at University of York in Chemistry?

FTE Category A staff submitted: 47.06

Research output data provided by the Research Excellence Framework (REF)

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