Investigating Nutrient-Dependent Regulation of Microglia Function and Immune Responses

• Funding – Tenovus Scotland funded 4-year studentship, providing tuition fees, training/research costs and an annual tax free stipend of £19,237, increasing annually according to the UKRI rate. 
• Start Date – Monday 9th September 2024
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.

Microglia are constantly sensing the brain environment for metabolic changes, damage and pathogenic invasion. Microglia are highly metabolically active, with activation in response to inflammatory stimulation increasing glycolytic demand. Changes in nutrient availability, such as in hypoglycaemia, leads to metabolic reprogramming of microglia via utilisation of glutamine and fatty acids to maintain their functional responses. Hyperglycaemia, due to poorly controlled diabetes, is associated with increased inflammation and risk of Alzheimer’s Disease (AD). It is unclear however, how changes in nutrient availability alter microglia inflammatory responses and proteomic reprogramming. 

This project aims to understand how key metabolic nutrients, glucose and glutamine, regulate microglia responses and function. By understanding how these nutrients are utilised by microglia, will be gain insight into how and why Type 2 Diabetes is a significant risk factor for the development of Alzheimer’s Disease. 

The aims of this PhD Project are as follows: 

1. To measure the rate of glucose and glutamine uptake in primary mouse microglia using fluorescent-labelled uptake assays under homeostasis and in response to the inflammatory stimuli to understand changes in metabolic demand over time and how this changes with inflammation
2. To understand how these metabolites are utilised in the proteome in homeostasis and inflammatory conditions by culturing microglia with 13C-labelled glucose and glutamine and perform mass spectrometry analysis
3. To generate detailed proteomes of microglia under homeostatic and inflammatory conditions in media deprived of/ in hyperabundance of glucose and glutamine 
4. To validate proteomic findings in post-mortem brain tissue sections from AD, AD + type 2 diabetes and controls using imaging mass cytometry and immunohistochemistry

Altogether, this project will provide a significant furthering in our understanding of the link between diabetes and AD by investigating the consequences of dysregulated nutrient homeostasis on microglia phenotype and function. 

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research.  We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.