PhD Studentship in Medicine

4 year PhD Studentship: Deciphering how domain organisation regulates heparan sulphate function

University of Nottingham, School of Medicine  

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

About the project  

This 4Yr PhD position is part of our BBSRC strategic Longer and Larger project, GlycoWeb (www.glycoweb.co.uk). The multi-partner project includes groups from The Universities of Nottingham, Liverpool and Manchester, and the Francis Crick Institute, as well as our international (USA and Denmark) partners.

GlycoWeb applies a diverse set of approaches to address the fundamental gaps in knowledge around glycosaminoglycans, using an ambitious multidisciplinary approach, integrating analyses at the transcriptional through to the multicellular level. The team assembled combines multiple approaches and innovations to work at the forefront of technological advances. 

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 GlycoWeb project and this PhD will focus on a specific part of that, 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. Novel breakthroughs in analytical methods (including those made by the GlycoWeb team) offer new opportunities to investigate how functional motifs are encoded in HS chains and how they influence their biological activity. Within GlycoWeb, we are using gastruloids as a model system with which to study GAG structure/function relationships. Gastruloids are generated from induced pluripotent stem cells (iPSCs) and create in vitro models with which we can study many of the critical steps of gastrulation and early development. We are creating iPSC lines with mutations in elements of the GAG biosynthetic machinery as well as using our novel GAG analytical technologies to investigate how changes in GAG structure and organisation drive and/or respond to shifting developmental stages. 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. 

The studentship will be based in the University of Nottingham Biodiscovery Institute, with access to a full range of equipment and laboratory facilities. We value diversity and welcome applications from people who from groups typically under-represented in academic research. Our labs and ways of working are built to be inclusive, with modifications that will support researchers with physical disabilities and/or those who are neurodivergent.

The project would suit someone with a desire to explore the biochemical composition and biological activity of GAGs. A good grounding in biochemistry/biology/chemistry/biophysics   is essential and you will need to be confident working with complex data.  We are a strong interdisciplinary group and a willingness to learn and work beyond your current comfort zone, supported by an excellent team, would be advantageous.

Eligibility

•           Project start date and duration: start 1st Oct 2025 for 48 months.

•           Due to funding restrictions, the position is only available to those eligible for UK home fees (see https://www.nottingham.ac.uk/fees/tuitionfees/202425/fee-regulations.aspx).

•           Candidates must possess or expect to obtain, a 2:1 or first-class degree in a discipline related to biochemistry, organic chemistry, biophysics or similar.

•           To apply,  

For any enquiries about the project and the funding please email: glycoweb@nottingham.ac.uk