PhD Studentship: Investigating Mechanisms of Neurodegeneration in Congenital Hyperinsulinism

Manchester Metropolitan University

Congenital Hyperinsulinism (CHI) is a rare inborn error of metabolism where the pancreas produces excessive insulin, resulting in persistently low blood sugar, leading to seizures and brain damage in newborn children. Our clinical partners at the Royal Manchester Children’s Hospital recognise that early diagnosis and prophylactic treatment with supplementary glucose substantially reduces brain damage during this critical post-natal period of neurodevelopment.

Earlier diagnostic biomarkers of neurodegeneration in CHI could substantially accelerate diagnosis and treatment. At Manchester Met, we have developed a human ‘brain-on-a-chip’ model that faithfully recapitulates the neurovascular unit, where neurons interface with the vasculature in the brain.

You will use CRISPR gene editing to introduce the most frequently occurring disease-causing mutation for CHI into induced Pluripotent Stem cells (iPSC). You will then be instructed in building the brain-on-a-chip model using iPSC to study the molecular mechanisms where genetic mutation, exposure to high insulin and low glucose combine to cause neurodegeneration in the brain. You will employ multiomic deep phenotyping to identify molecular alterations that relate to CHI and principally evaluate their fit as biomarkers for CHI diagnostics. This project will provide training in gene editing, iPSC technologies, and complex cell models with a focus on clinical unmet needs.

Project aims and objectives

The aim of this project is to comprehensively evaluate the combined effects of ABCC8 gene mutation, high circulating insulin and low circulating glucose to neurodegeneration in CHI.

Objectives:

• Introduce CHI pathogenic mutations to the ABCC8 gene in iPSC using CRISPR gene editing.
• Apply CHI iPSC to create a brain-on-a-chip model.
• Evaluate individually and combinatorially the effects of ABCC8 mutation, high insulin and low glucose in causing neurodegeneration using the brain-on-a-chip model.
• Conduct a transcriptomic and proteomic evaluation of CHI versus control conditions to identify putative biomarkers.

Funding

Only Home students can apply. Home tuition fees will be covered for the duration of the 3-year project.

The student will receive a standard stipend payment for the duration of the award. These payments are set at a level determined by the UKRI, currently £20,780 for the academic year 2025/26.

Specific requirements of the candidate

The qualifications, skills, knowledge and experience applicants should have for this project, in addition to our standard entry requirements.

Requirements include:

• A 1st or 2:1 degree in a relevant undergraduate degree.
• Experience of mammalian cell culture.

How to apply

Interested applicants should contact Prof Tristan McKay (t.mckay@mmu.ac.uk) for an informal discussion.

To apply, you will need to complete the online application form for a full-time PhD (or download the PGR application form) in the Department of Life Sciences.

Please include your CV and a cover letter addressing the project’s aims and objectives, demonstrating how the skills you have map to the area of research and why you see this area as being of importance and interest.

If applying online, you will need to upload your statement in the supporting documents section, or email the application form and statement to PGRAdmissions@mmu.ac.uk.

Closing date: 16th December 2025

Expected start date: April 2026.

Please quote the reference: SciEng-TM-April 2026-Congenital Hyperinsulinism