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Project

Analyzing the regulation of synaptic vesicle mobility by pre-synaptic liquid phase-separation in health and disease

 Tauopathies are characterised by accumulation of Tau protein in the neurons which causes synaptic dysfunction and synapse loss, and consequently neuronal death. Recent studies show synaptic loss occurs earlier than neuronal death in the progression of the neurodegenerative disorders and its contribution to the pathophysiology of the disease will be important to investigate. Previously the Verstreken lab showed that pathogenic Tau protein localises into the pre-synapses, binds to the synaptic vesicles via Synaptogyrin-3 and interferes with the mobility of the synaptic vesicles. However, the mechanism of this reduced synaptic mobility and how it relates to synapse loss and neurodegeneration is not clear. Previous studies showed that the synaptic vesicle(SV) pool exist in Synapsin-mediated liquid-liquid phase separated condensates. One possibility is that the additional interactions of Tau-Synaptogyrin-3 may interfere with Synapsin-mediated SV condensates and contribute to synapse loss and neurodegeneration. In this project, the effect of Tau-Synaptogyrin-3 interaction on phase separated synaptic vesicle pool and its effect on synaptic survival in the context of neurodegeneration will be investigated.

Date:7 Mar 2022 →  Today
Keywords:Synapse, phase separation
Disciplines:Neurological and neuromuscular diseases
Project type:PhD project