Assessing the Role of Tau in Synaptic Architecture and Function

As we are living in an ageing population, the prevalence of cognitive, sensory and motor decline, as well as neurodegenerative diseases such as Alzheimer's disease (AD) and Fronto-Temporal Dementia (FTD), is increasing.
Synapses are specialised cell junctions which contain complex machinery to allow the transmission of signals from neuron to neuron. During ageing and neurodegenerative disease, the synaptic machinery is disrupted. This leads to changes in neuronal networks, followed by cognitive, sensory and motor decline. However, the underlying causes of these changes to synaptic machinery are not well understood. To help answer this question, the project will study novel roles of Tau in regulating synapses.
Tau is a protein which plays a key role in the development of many neurodegenerative disorders including AD and some forms of FTD. These disorders, known as the Tauopathies, arise from mutations in Tau or the dysregulation of the protein itself. Besides Tau's role in neurodegenerative disease, Tau mis-localisation and aggregation are also hallmarks of the ageing brain. Taken together, Tau could be an ideal therapeutic target for the development of treatments of age-related cognitive decline, AD and FTD.
Considering Tau's roles in the pathogenesis of dementia and its potential as treatment, understanding its physiological function is vital. Tau loss has been known to lead to age-related synaptic deficits in mice and the fruit fly Drosophila by triggering microtubule and axonal transport aberrations, affecting synapse formation and maintenance. A recent proteomics study from the lab identified that Tau binds to a complex array of factors that are important in regulating synaptic function. My project will be studying the roles of Tau in synaptic architecture by investigating its relation to novel interacting proteins identified in the proteomics study. The project will be using Drosophila as the model organism for its genetic amenability, powerful experimental strategies and robust behavioural assays.