Understanding the role of organelle contact networks in neuronal health and disease

Deciphering how neuronal transmission and circuit formation enable movement, thought, and behaviour, represents one of the central challenges of research today. Much of this work has focussed on characterising communication between neurons. However, within each individual neuron is an equally complex communication network between subcellular organelles. Membrane contact sites between organelles are now recognised as key sites that enable the rapid transfer of biomolecules across the organelle interaction network and thereby facilitate successful action potential firing, synaptic vesicle release, and synaptic membrane organisation. However, the machinery and mechanisms that regulate contact sites to enable neuronal function remain unknown. My lab will deploy the unique imaging, proteomic and lipidomic tools that I have developed to explore the role that organelle contacts play in neuronal transmission and circuit formation, and discover how these processes are compromised during neurodegeneration. To achieve this we will investigate: - The role of molecular tethers in dictating where and when contact sites form between different organelles in healthy and diseased neurons - The mechanisms and machinery underpinning the exchange of key biomolecules at neuronal organelle contact sites, and how these processes are corrupted during neurodegeneration. - How these processes converge to enable neuronal transmission and circuit formation