The Role of the Endosomal System in Alzheimer’s Disease.

Description

Summary of the project

Neurodegenerative disorders, including Alzheimer’s disease, are a global public health priority, affecting millions of people worldwide. Despite decades of research into these disorders we are still in urgent need of early-stage diagnostic markers and new therapeutic targets. This PhD project will aim to meet these needs through understanding the role of the endosomal system in Alzheimer’s disease.

The endosomal system comprises a series of intracellular membrane-bound compartments controlling protein and lipid transport. Perturbation of the endosomal system has been implicated in the initiation and progression of Alzheimer’s disease, with neuronal endosomal swelling classed as an early hallmark of disease. Crucially, the role of the endosomal system in glial cells in Alzheimer’s disease is unclear and understudied, leaving a critical gap in our knowledge of pathology. Astrocytes, a form of glial cells, are known to play an essential role in neuronal health and Alzheimer’s pathology, raising the question of whether endosomal dysfunction in astrocytes, could be inducing neuronal death and neurodegeneration.

Dr McMillan’s recent work has identified important astrocytic proteins that depend on the endosomal system for their expression and localisation. The aim of this PhD project will be to determine how impairment of the endosomal trafficking of these proteins affects astrocytic, and thereby neuronal function. The project will use cutting edge technologies in proteomics, cell biology and biochemistry across a range of models including cell lines, rat primary astrocytes, human brain tissue, and through collaboration human-derived astrocytes.

The student will be supervised by Dr Kirsty McMillan, a new group leader in the Institute of Systems, Molecular and Integrative Biology (ISMIB) in the University of Liverpool. ISMIB is a world-leading Institute in multi-omic research, fundamental cell biology and cell signalling with excellent shared facilities including the Centre for Proteome Research, the Liverpool Centre for Cell Imaging, and the Biobank. Collaborative input and supervision will be provided by Professor Sylvie Urbé (University of Liverpool), and Professor Heather Mortiboys (University of Sheffield).

This position is available to start immediately (with a flexible start date until October 2025). We encourage applications from enthusiastic and motivated candidates with a BSc (minimum upper second-class Honours degree), master’s degree or equivalent in Neuroscience, Biochemistry, Biological Sciences or related discipline. Advanced training in cell biology, proteomics and biochemical approaches will be provided.

Informal enquiries are very welcome and can be sent directly by email to Dr Kirsty McMillan (kirsty.mcmillan@liverpool.ac.uk).

Applications should be made to Dr Kirsty McMillan (kirsty.mcmillan@liverpool.ac.uk) in the first instance. Please include your CV, a personal statement outlining your interest in the position and two reference letters. This is for all applications. Only when a candidate has been selected following interview will a formal online application be required.

Supervisors: Dr Kirsty McMillan (kirsty.mcmillan@liverpool.ac.uk) with collaborative input from Professor Sylvie Urbé (University of Liverpool) and Professor Heather Mortiboys (University of Sheffield).

Keywords: Molecular biology, Endosomal Trafficking, Astrocytes, Neurodegeneration, Alzheimer’s Disease, Liverpool, United Kingdom.