Dementia, including Alzheimer’s disease, affects around 850,000 people in the UK. At the moment, there are very few treatments to ease symptoms, and there is still no cure. This places a heavy emotional and financial burden on families, the NHS, and wider society. One reason for this is that we still do not fully understand what causes nerve cells in the brain to degenerate, although we know that a person’s genes play an important role.
Nerve cells communicate with each other through long, thin structures called axons, which act like cables which propagate information throughout the brain. These axons need to remain healthy throughout a person’s life, even when faced with challenges such as physical stress, infections, or genetic variations. In many neurodegenerative diseases, axon morphology becomes abnormal, which can contribute to the development and progression of the disease.
By studying how genes help keep axons healthy, scientists can learn more about how these diseases start and develop, and potentially identify new ways to treat them.
This project uses a tiny, transparent worm called Caenorhabditis elegans as a model. Despite its simplicity, this organism shares many important biological features with humans. Using this model, the project will explore the genes that are necessary to maintain the shape and health of axons.
Axonal dysfunction has long been implicated in neurodegenerative diseases, as axonopathies are a consistent finding in patients, yet the mechanisms maintaining axon morphology during ageing remain poorly understood, preventing further development of potentially revolutionary cures.
While cytoskeletal components are known to support axonal integrity, the extracellular and intracellular signalling pathways involved are less clear. My preliminary work, using the model system C. elegans, has identified novel pathways, specifically TGF-β and autophagy, which influence axon morphology and potentially offer new therapeutic targets.
This project aims to uncover the roles of those two pathways in the maintenance of axon morphology, but also the project aims at finding the genetic factors and structural components critical for axon morphology using C. elegans.
AMS Springboard Award