Background
Carbohydrates, glycans, are central to human life. They coat our cells, acting as molecular bar-codes; they are the “language of the cell”. They modulate cellular communication. Yet, frequently these glycan codes are disrupted in disease, high jacked by pathogens and the enzymes involved in synthesis and degradation are frequently linked to genetic disease, including lysosomal storage and viral diseases. The degradation of glycans is central to many biotechnology industries including renewable energy. But glycans are complex, and precision tools are needed for their study. Your work will enable their development and application.
Activity-based probes are a branch of chemical genetics, which allow the specific inhibition, capture and imaging of enzymes. As part of a three-country team, funded through a European Research Council (ERC) Synergy Grant, the project seeks to apply activity-based chemical probes across many disciplines, from health to sustainable energy.
This 3 Year ERC studentship is offered in the laboratories of Gideon Davies, FRS at the University of York, featuring possibilities for external placements in Leiden or Barcelona. The PhD position will use structural biology techniques to study activity based probes of enzymes involved in glycan biosynthesis and modification, including medicine and plant polysaccharide degradation (the project can be tailored to student’s interests).
Objectives
To clone express and characterize human and fungal/bacterial glycosidases and glycosyltransferases involved in disease and to characterise novel activity-based probes and imaging agents targeted at these. Probes will allow enzyme imaging, inhibition, and provide a mechanism for enzyme discovery.
Experimental Approach
Working with synthetic colleagues in Leiden, and computational experts in Barcelona, you will clone and express genes encoding human and fungal/bacterial carbohydrate-active enzymes, characterize the proteins, solve their 3D structures in complex with ligands and activity-based probes and use these probes to measure enzyme levels in cellular extracts and secretomes. You will collaborate on the design and analysis of new, bespoke, inhibitors and probes based upon your observations and apply these in cellular models of disease and/or biotechnological contexts.
Novelty Activity-based probes (see https://tinyurl.com/y57vg7ac) are a transformative precision tool in modern chemical biology allowing visualisation of specific enzymes in complex samples.
Training
As part of York’s, world-renown “York Structural Biology Laboratory (YSBL), you will receive training in molecular biology and protein production, protein characterization, enzyme kinetics and modern structural biology (primarily X-ray, but also CryoEM where appropriate). You will collaborate with Dutch and Spanish groups as part of the dynamic “Carbocentre” team which covers many aspects of activity-based probe research.
All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills: https://www.york.ac.uk/chemistry/postgraduate/training/idtc/
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: https://www.york.ac.uk/chemistry/ed/.
For more information about the project, click on the supervisor's name above to email the supervisor. For more information about the application process or funding, please click on email institution
This PhD will formally start on 1 October 2023. Induction activities may start a few days earlier. An earlier start date may be possible.
To apply for this project, submit an online PhD in Chemistry application: https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPCHESCHE3
You should 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/
Continue with Facebook
