Assessing the “when” and “why” of synapse loss in neurodegenerative disease.

Maintaining synaptic health is essential for normal brain function, however this process breaks down early in dementia-causing diseases. If we understand where, when and why synapses are lost, we may be able to develop therapeutics to keep them safe and stop dementia in its earliest stages. This would have significant societal impact, as dementia already affects nearly 1 million people in the UK and costs >£35 billion per year.

 We recently showed, for the first time, that synapse loss in the frontal cortex of Amyotrophic Lateral Sclerosis (ALS) patients associates with cognitive decline (1) (present in more than 50% of patients (2)) and others have shown synapse loss in fronto-temporal dementia (FTD) patients with similar cognitive changes (3), providing clues as to “where” synapses are lost and reinforcing a mechanistic overlap between dementia and ALS.

 Building on this observation of synapse loss in ALS patients, we now want to explore in more detail “when” and “why” synapses are lost. This PhD project will address these questions and focus on the role of a key pathological protein in dementia, called TDP-43.

 The student will help develop and maintain fruit fly models of disease, allowing us to assess the impact of protein changes on synaptic anatomy and disease progression. Human post-mortem material will be characterised at synaptic resolution to understand the nature of synaptic vulnerability in human disease. Furthermore, other model systems will be used to assess the temporal profile of synapse change in disease. The student will benefit from our expertise in high-resolution synaptic imaging (1) and proteomics (4, 5) to characterise the impact of protein changes on synapse health.

 It is essential that candidates have a solid background in neuroscience/neurodegeneration and are keen to learn new techniques and apply their own experience to the role. It is expected that candidates have achieved or expected to achieve a 1st class or upper 2nd class degree in a relevant biomedical sciences subject. Experience using any of the techniques or models described above would be beneficial, but not essential.

 This exciting project is supported by a recent Alzheimer’s Society Fellowship award to Dr. Chris Henstridge and is funded for 4 years.

This PhD opportunity is for UK students only.

Diversity statement

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.