Anglia Ruskin University ARU Featured PhD Programmes
European Molecular Biology Laboratory (Heidelberg) Featured PhD Programmes

Chemical probes for the study of carbohydrate-active enzymes


Department of Chemistry

About the Project

Background

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 glycans of very complex and diverse structures. They can also be linked to other biomolecules such as proteins, a modification referred to as glycosylation. Since glycans are not directly genetically encoded, their levels and structures are dynamic and at any given time the exact composition of glycans is dictated by the networks of cellular enzymes that create and modify them. Defects in the functioning of one of these enzymes often leads to disease, however the mechanisms by which the malfunctioning of individual enzymes leads to specific pathologies are often poorly understood.

In our group we focus on the development of novel chemical tools to advance our understanding of carbohydrate biology: in specific we are interested in studying how specific carbohydrate-processing enzymes work, both at the molecular level as well as in terms of their functioning in a cellular environment and their role in pathology. This project contributes to our work program by designing, synthesising and testing novel enzyme probes for application in structural biology and/or cell biology experiments.

Objectives

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, you will focus on a set of enzymes responsible for the biosynthesis of O-mannosylated proteins. You will develop substrate analogues as tools to study these enzymes, either by inhibiting their function or by enabling unnatural functionalities to be introduced that allow us to characterise and visualise the chemical process catalysed by the target enzyme in vitro or inside cells. The project is of a multidisciplinary nature and will be tailored to your specific experience, interests and training aspirations. For example, the synthesised probes may be tested in living cells, on isolated proteins in vitro, or in combination with structural protein work.

Training

Working on this project, you will be able to strengthen your knowledge and skills in a variety of methods and techniques in synthetic chemistry, cell biology, molecular biology, biochemistry and/or protein crystallography. Specifically, depending on the exact nature of the project, you may be exposed to project specific training in cloning, bacterial and/or mammalian cell culture, protein expression in either of these systems, enzyme activity assays, SDS-PAGE and immunoblotting, affinity purification, mass spectrometry analysis, fluorescence microscopy and/or FACS, in addition to the various analytical techniques associated with organic synthesis such as HPLC purification, LCMS and NMR characterization.

In addition, 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 as well as 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.

Equality and Diversity

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.

Your background
You should expect hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a related subject. Please check the entry requirements for your country: https://www.york.ac.uk/study/international/your-country/

Funding Notes

This project is available to students from any country who can fund their own studies. The Department of Chemistry at the University of York is pleased to offer Wild Fund Scholarships. Applications are welcomed from those who meet the PhD entry criteria from any country outside the UK. Scholarships will be awarded on supervisor support, academic merit, country of origin, expressed financial need and departmental strategy. For further details and deadlines, please see our website: View Website

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here

The information you submit to University of York will only be used by them or their data partners to deal with your enquiry, according to their privacy notice. For more information on how we use and store your data, please read our privacy statement.

* required field

Your enquiry has been emailed successfully



Search Suggestions

Search Suggestions

Based on your current searches we recommend the following search filters.



FindAPhD. Copyright 2005-2021
All rights reserved.