Role of MuSK signalling in the adaptive regeneration of the neuromuscular synapse
Muscle Specific Kinase (MuSK) is a tyrosine kinase that mediates the formation of neuromuscular synapses during development. This project will probe the potential of MuSK signalling to regenerate synaptic structure and function when neuromuscular synapses are challenged by motor neuron disease and myasthenia gravis.
The loss of synapses is a feature of many forms of neurodegeneration. In motor neuron disease and in normal aging the loss of neuromuscular synapses leads to weakness and the eventual death of the motor neurons. Muscle Specific Kinase (MuSK) helps organise the pre- and postsynaptic differentiation of the neuromuscular synapse during embryonic development. This project will use recombinant Adeno-Associated Virus (rAAV) to overexpress wild-type and mutant MuSK (and other proteins of the MuSK pathway) in muscle fibres of living mice. This will be done to elevate and suppress (respectively) the level of MuSK tyrosine kinase signaling at the postsynaptic membrane. Electrophysiological recordings and confocal microscopy will be used to test how this signalling system helps the neuromuscular synapse to adapt to the challenge of disease in mouse models of myasthenia gravis and motor neuron disease. This project will help to clarify the potential of the MuSK kinase system as a therapeutic target for protecting synapses in myasthenia gravis, sedentary aging and in motor neuron disease.
This co-supervisor for this project is Associate Professor Peter Noakes from the University of Queensland
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The opportunity ID for this research opportunity is: 16
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