Student projects - Neuromotor control
The Noakes lab has a number of research projects that are suitable for Summer, Advanced Science, Honours, MSc (lab Rotations), and PhD students.
1) NEUROMOTOR: Electrophysiology and imaging based projects – This project revolves around the neuro-motor system. Specifically we are interested in determining the roles of glycine and GABA on motor neuron development – which includes motor neuron activity – morphology- and numbers.
We are also interested our neuromotor research into how the neuromotor system adapts with age. Specifically, how do motor neurons and their central and peripheral synapses change in aging mice.
2) NEUROMUSCULAR: We have a number of projects centred on trans-synaptic signalling in the formation and maintenance of pre-and post synaptic specializations. These include:
i) The role of adhesive molecules (the synaptic laminins) in the formation of voltage gate-active zone complexes (pre-synaptic release sites) at neuromuscular synapses. Synaptic laminins bind to the pore forming subunits of specific voltage gated calcium channels; we are looking at the location and function of these channels in mutant mice missing selected laminin isoforms.
ii) The roles of agrin and neuregulin in the modulation of post-synaptic specializations during development and during ageing – neuregulin-1 appears to have short and long term actions on agrin’s ability to cluster and maintain high density clusters of acetylcholine receptors within post-synaptic specializations. These actions appear to be independent of neuregulin’s known gene activation pathways. For these studies, we employ a combination of in vitro bioassays, and in vivo experiments using a variety of transgenic mice.
iii) The functional consequences in perturbations to trans-synaptic signalling at neuromuscular synapses. These projects centre on the electrophysiological analyses of mice missing selected synaptic signalling molecules. It includes imaging of calcium influxes into motor nerve terminals and their capping Schwann cells.
3) NEUROIMMUNOLOGY: We have a host of projects investigating the role of specific innate immune molecules in the normal development (e.g. synapses) and in the diseased nervous system. Specifically we are interested in complement molecules C3a, C5a and their receptors during periods of naturally occurring motoneuron cell death, and during adult motoneuron cell death (e.g. Motor Neuron Cell Death/ALS; Spinal Muscular Atrophy). Our previous work has shown that if we block the receptor for C5a – CD88 we can slow down the death of adult motor neurons in animal models exhibiting motor neuron disease. Blocking of CD88 appears to block the proliferation-activation of surrounding glial cells – how this is achieved is not known. Interestingly C5 and it receptors are also present on normal motoneurons but become unregulated during disease – how this contributes to neuronal death is not known. Finally C5a has a second receptor C5L2 – it too is expressed on neurons and glia – its function in normal neuronal development and during death is also not known. These projects use in-vitro bioassays (motor neurons, and glial cells) and transgenic animal models motor neuron disease – SOD1 and TDP43 transgenic mice.