MSc by Research: Investigating Glycogen-Dependent Regulation of Microglia Inflammatory Responses

About the Project

Microglia are the resident immune cells of the central nervous system, responsible for responding to infection and damage in a protective manner. In Alzheimer’s Disease, microglia responses are dysregulated, leading to chronic inflammation and failure to protect the brain from neurodegeneration. Understanding how and microglia transition from neuroprotective cells to those that drive neurodegeneration is vital to further our understanding of the molecular and cellular basis of inflammation in neurodegenerative diseases. Inflammation is tightly regulated by metabolic programming, with microglia switching from oxidative phosphorylation to glycolysis under inflammatory conditions, including in response to amyloid beta, a protein aggregate and major pathogenic hallmark of Alzheimer’s Disease. Initially, microglia are highly efficient at phagocytosing amyloid beta, however this ability diminishes over time, leading to functional and metabolic exhaustion. It is therefore important to understand the molecular basis of metabolic exhaustion in microglia to be able to develop novel strategies for reviving microglia functions.

Proteomic analysis from our lab of microglia from an Alzheimer’s Disease-like mouse model has identified increased glycolytic activity during disease progression that is associated with glycogen degradation, rather than increased glucose transport, suggesting that glycogen plays a key role in regulating microglia metabolic and inflammatory responses. As previous findings have shown that sustained glycolysis leads to microglia dysfunction and metabolic exhaustion, our hypothesis is that metabolic exhaustion of microglia corresponds to depleted glycogen stores. We therefore aim to investigate this further by using molecular tools to understand the role of glycogen in driving inflammatory responses, and the proteomic basis of amyloid-induced metabolic exhaustion in microglia.

This project will use primary mouse and human iPSC microglia to investigate glycogen-dependent regulation of microglia in vitro. We will expose microglia to pathogenic forms of amyloid beta and measure changes in glycolysis and glycogen utilization over time. Furthermore, we will investigate the importance of glycogen in regulating immune responses by inhibiting its breakdown and performing detailed proteomic analysis to identify glycogen-mediated pathway activation. Altogether this project will provide important understanding of the molecular basis of glycogen regulation of inflammatory responses of microglia, and the molecular basis of metabolic exhaustion.

In this project the following skills will be acquired:

• In vitro culture of primary mouse and hiPSC microglia
• Uptake assays
• Flow Cytometry
• Western Blotting
• Mass Spectrometry
• Proteome analysis and Bioinformatics

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.

Please see our website for further details on the programme and how to apply: Life Sciences MSc by Research MSc by Research (Postgraduate) : Study : University of Dundee

Please note before submitting your application that you must list your top three project choices in the Research Proposal section of the application form.

When you complete your application form, you should include your top 3 project choices, 2 letters of reference, uploaded under "Other Information" > "Supporting documents" and a personal statement. Failure to do so will delay your application.

Please note when submitting an application, please note our intake deadlines on the how to apply section of our website.