SSA:Neuronal control of mitochondrial trafficking down long-range axons

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To support the energy demands of synaptic transmission, neurons have many thousands ofmitochondria located along their highly branched and very long axons. Throughout a neuron's entirelifetime, it must solve the unique cell biological problem of delivering these mitochondria to thecorrect axonal locations. Mitochondria are known to move around within axons and mitochondrialdistribution is affected in many neurological diseases, which tells us that that this is a highly regulatedand important process. However, we do not how neurons control mitochondrial movement in axonswithin the brain, or how this influences their overall distribution. In this project, we will combine invivo 2-photon imaging of neuronal mitochondria with computational modelling to solve how neuronalactivity controls the delivery and distribution of mitochondria in axons that is fundamental to everyneuron in the brain.In the Ashby lab, we have developed in vivo 2-photon microscopy techniques to track individualmitochondria in neurons of the living mouse brain over the course of minutes through to days. Usingthese approaches in this project will allow us to define how mitochondria move around functioningaxons and how that movement is controlled by neuronal activity. We will then test whether theselocal trafficking rules can explain how mitochondria end up distributed across the axon. To do this,extending previous approaches by the O'Donnell lab, we will build sophisticated computationalmodels of anatomically real neurons that simulate the trafficking of mitochondria across the entireaxonal tree. By pulling together the power of the in vivo measurements and the large scale of thecomputational models, we will define how neurons overcome the challenge of ensuring they have theright numbers of mitochondria in the right place to maintain their function.This is an interdisciplinary project that is built on the close collaboration between the Ashby andO'Donnell labs. The nature of the project means that the student will receive training in a wide-rangeof technical skills ranging from cutting edge imaging to in vivo experimental skills and coding forcomputational neuroscience.