PhD Opportunity – EASTBIO: Serum Albumin Glycation and its Impact on Zinc-Dependent Haemostatic Pathways and Insulin Dynamics
Project Title:
EASTBIO: Serum Albumin Glycation and its Impact on Zinc-Dependent Haemostatic Pathways and Insulin Dynamics
Supervisor(s):
Principal Supervisor: Dr Alan Stewart (University of St Andrews, School of Medicine), [email protected]
Co-supervisors: Prof. Carlos Penedo (University of St Andrews, Schools of Physics & Astronomy and Biology), [email protected]
Deadline:
Monday 15 December 2025
Project Description:
Zinc is a crucial trace element required for the structure and function of thousands of proteins across biological systems. Because free Zn²⁺ ions are potentially harmful at elevated concentrations, organisms have evolved tight control mechanisms to buffer and transport zinc. In the bloodstream, this role is primarily fulfilled by human serum albumin (HSA), which binds Zn²⁺ and regulates its availability.
Beyond general transport, Zn²⁺ contributes to dynamic biological processes such as protein–protein interactions and structural transitions. For example, Zn²⁺ is released from cells and platelets during activation, where it modulates protein assembly involved in clot formation. The concentration of free Zn²⁺ in plasma can influence how much zinc is taken up by platelets and how it is distributed within them. Perturbations in plasma Zn²⁺ levels—such as those caused by changes in albumin structure—can therefore affect these processes.
One such structural change is glycation, a non-enzymatic modification of proteins that occurs under conditions of elevated glucose. Glycation of albumin has been shown to reduce its affinity for Zn²⁺ (Iqbal et al., 2018), potentially altering zinc buffering capacity and downstream biological effects.
Zinc also plays a key role in insulin biology. Inside pancreatic β-cells, insulin is stored as a Zn²⁺-coordinated hexamer (Zn₂Ins₆), which is inactive. Upon secretion, insulin remains in this hexameric form until Zn²⁺ dissociates, allowing monomeric insulin to interact with its receptor. Albumin facilitates this dissociation by binding Zn²⁺, promoting the transition from inactive to active insulin (Pertusa et al., 2017). If glycation reduces albumin’s ability to bind Zn²⁺, this could interfere with insulin activation and signalling.
Hypothesis: Glycation alters the zinc-binding properties of albumin, with consequences for both protein assembly in clotting and insulin activation.
Objectives:
1. Characterise zinc binding and structural changes in glycated albumin using biophysical techniques (e.g., ITC, mass spectrometry).
2. Investigate how glycation affects protein assembly during fibrin formation using functional and imaging approaches.
3. Examine the impact of glycation on insulin hexamer dissociation using fluorescence-based methods.
This project aims to uncover how a single molecular modification—albumin glycation—can influence zinc-dependent biological processes central to protein structure, signalling, and regulation.
Funding Details:
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate and UK level tuition fees. The University of St Andrews will cover the Home-International fee difference.
How to Apply:
Application instructions can be found on the EASTBIO website- How to Apply | EastBio Doctoral Training Partnership | Biology
1) Download and complete the Equality, Diversity and Inclusion survey.
2) Download and complete the EASTBIO Application Form.
3) Please complete an application on our online portal: How to apply – Study at St Andrews – University of St Andrews
4) Select the course ‘PhD with internship’
5) Your online application must include the following documents:
– Completed EASTBIO application form
– Academic Qualifications
– English Language Qualification (if applicable)
– 2 References: this must be completed on the EASTBIO Reference Form, also found on the EASTBIO website
Please download the EASTBIO reference form and send it to your referees. They can either upload it directly to the portal using the automated email they will receive, or they can email it to Rachel at [email protected].
Contact:
Queries on the project can be directed to the project supervisor.
Queries on the application process can be directed to Rachel Horn at [email protected].
UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website.