4 Year PhD Studentship: Deciphering How Domain Organisation Regulates Heparan Sulphate Function

Supervisors: Professor Cathy Merry, Professor Kenton Arkill, Dr. Andrew Hook

Overview

Glycosaminoglycans (GAGs) are linear sugars that are displayed on all cells throughout the body as well as in the matrix. Like other glycans, they are not built against a defined template, and yet their structure is non-random, with specific motifs within the glycan chains defining binding sites for critical signalling and structural molecules. Unravelling the ways in which these motifs are encoded into GAGs by their biosynthetic machinery is the fundamental challenge behind the BBSRC-funded GlycoWeb project. This 4-year PhD forms part of GlycoWeb’s broader mission.

Project

The PhD project will focus on the organisation of highly sulphated domains within the heparan sulphate (HS) GAG family. These sulphated domains typically bind to protein ligands via sulphated residues that interact with positively charged regions within the protein ligand(s).  The 3D organisation of these domains is therefore critical for their function. The object of our studies is to gain a fundamental understanding of this incredible family of glycans, opening the potential to use that knowledge to design new drugs, new biomaterials or to identify new therapeutic opportunities.

What you’ll do

You will receive training and hands-on experience in:

• Investigating how functional motifs are encoded in HS chains and how they influence their biological activity.

• Using gastruloids as a model system with which to study GAG structure/function relationships.
• Generating gastruloids from induced pluripotent stem cells (iPSCs) to create in vitro models for studying critical steps of gastrulation and early development.
• Creating iPSC lines with mutations in elements of the GAG biosynthetic machinery.
• Applying novel GAG analytical technologies to investigate how changes in GAG structure and organisation drive and/or respond to shifting developmental stages.

Working Environment:

• Based at the Biodiscovery Institute at UoN, a multidisciplinary centre with advanced laboratory and imaging facilities
• Access to a full range of equipment and laboratory facilities
• Inclusive and supportive lab culture with flexible working practices
• Applications welcome from candidates from under-represented backgrounds
• Adjustments available to support candidates with physical disabilities or neurodivergence

You’ll be a good fit if you:

• Have a background in Biochemistry, biomedical sciences, organic chemistry and biophysics
• Are desire to explore the biochemical composition and biological activity of GAGs
• Are confident working with complex data
• Enjoy learning beyond your current expertise with the support of our excellent interdisciplinary team

Eligibility

• Start date: 1^st October 2025
• Open to applicants eligible for UK home tuition fees only (check eligibility)
• Applicants must hold (or expect to receive) at least a 2:1 undergraduate degree in a relevant discipline
• The four year studentship comprises UK home tuition fees, a tax-free stipend of £20,780 per year and a generous consumable funding to support research

Cover Letter, CV and academic transcripts for application and Informal enquiries may be addressed to: GlycoWeb@nottingham.ac.uk

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