Peter G. Noakes is investigating the cell and molecular mechanisms that underlie the development and breakdown of the neuro-motor system. His lab works on the following: 1) cell and molecular mechanisms surrounding the establishment of neuromuscular and motor neuron (CNS) synapses, including electrophysiology. 2) The generation and development of motoneurons in health and in disease (e.g. motor neuron disease {ALS}). 3) The role of innate immune system in motor neuron health and disease. His lab employs biochemistry, immuno-histology, electrophysiology, live cell imaging, behaviour, cell and molecular biology to study these issues.

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Students

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.

  1. Fogarty MJ, Smallcombe KL, Yanagawa Y, Obata K, Bellingham MC, and Noakes P.G.. (2013) Genetic Deficiency of GABA Differentially Regulates Respiratory and Non-Respiratory Motor Neuron Development. Ms. No. PONE-D-12-34918R1. To be published PLOS ONE on February 15, 2013.
  2. Narayanan RK, Mangelsdorf ME, Panwar A, Butler TJ, Noakes PG, and Wallace RH. Identification of RNA bound to the TDP-43 ribonucleoprotein complex in the adult mouse brain. Amyotrophic Lateral Sclerosis and Frontotemproal Degeneration. (2012). 2012 Oct 24. [Epub ahead of print] PMID: 23134510.
  3. Lee JD, Lee JY, Taylor SM, Noakes PG and Woodruff TM. Innate Immunity in ALS Amyotrophic Lateral Sclerosis, Editor Mh Maurer. (2012) pp: 393-412. (Book/Chapter).
  4. Ngo, S.T., Cole, R.N., Sunn, N., Phillips, W.D. and Noakes, PG. Neuregulin potentiates agrin-induced acetylcholine receptor clustering via muscle specific kinase phosphorylation. Journal of Cell Science (2012) 125: 1531-1543.
  5. Ghazanfari N, Fernandez KJ, Murata Y, Morsch M, Ngo ST, Reddel SW, Noakes PG, Phillips WD. Muscle Specific Kinase: Organiser of synaptic membrane domains. International Journal of Biochemistry and Cell Biology (2011) 43: 295-298.

Find out more about our research environment and how to apply to do a short or long-term research project with us.