Professor Lizzie Coulson did her undergraduate Honours degree at the University of Melbourne, majoring in Genetics and Biochemistry. Her PhD (1997) in the Department of Pathology, University of Melbourne, with Professor Colin Masters, was on the normal function of the amyloid precursor protein of Alzheimer’s disease. Following a year at the ZMBH, University of Heidelberg, Germany, she pursued postdoctoral work studying neuronal cell death in neurodegeneration and development at the Walter and Eliza Hall Institute before being recruited in 2003 to the University of Queensland as a founding member of the Queensland Brain Institute.
As the fastest growing segment of our population is that which includes individuals over the age of 60, the burden of neurodegenerative conditions, such as Alzheimer’s disease, motor neuron disease and stroke, represents a compounding medical and societal challenge. The laboratory's primary research goal is to identify and characterise the regulators of neurodegeneration and neuronal death in order to increase our understanding of molecular mechanisms. The longer-term goal is to translate these findings into candidate therapeutics to treat neurodegenerative diseases. The focus has been to characterise the cell death signalling pathway mediated by the p75 neurotrophin receptor (p75NTR), a neural death receptor which is activated in a number of neurodegenerative conditions including Alzheimer's disease and motor neuron disease. The specific aims capitalise on the laboratory's expertise in studying the structure and function of p75NTR.
Role of p75NTR in neurodegenerative disease.
The laboratory recently reported that p75NTR death signalling can be promoted by amyloid-ß peptide that characteristically accumulates in Alzheimer’s disease. We are investigating the regulation and activation of p75NTR death signalling in cholinergic neurons in this condition, and testing whether disrupting p75NTR function can prevent cholinergic degeneration, and cognitive decline, in animal models. As an extension of this work we are developing methods to assess cholinergic degeneration and amyloid plaque deposition in animal models of Alzheimer’s disease by magnetic resonance imaging (MRI).
How neurotransmitter- and neurotrophin-mediated signals determine cell survival.
We are investigating the basic molecular mechanisms by which neurotransmitter receptor activation and receptor trafficking affect p75NTR activation and subsequent death signalling using molecular and biochemical techniques in in vitro and in vivo models. We are also investigating the role of p75NTR cleavage in promoting death signalling, using confocal microscopy techniques to image live cells and cell membranes in real time. This project will lead to a greater understanding of p75NTR biology, and will also provide knowledge of the kinetics of p75NTR-mediated death signals and the time frame within which they can be inhibited.
- Professor Anders Nykjaer - Aarhus University, Denmark
- Associate Professor Jakob Hort - Charles University, Prague, Czech Republic
- Associate Professor Stephen Rose - UQCCR
- Professor Pankaj Sah - QBI
- Professor Fred Meunier - QBI
- Professor Maree Smith - Pharmacy
- Professor Ian Brereton - CAI
- Professor Andrew Wittaker - CAI
Possible PhD Research Projects (Updated August 2014)
- How important is regulated intramembranous cleavage in p75 function? (molecular biology, transgenic and viral manipulation of gene expression, histology)
- The role of p75NTR in developmental and adult neurogenesis? (stem cells, cell culture, transgenic animals, histology)
- What is the mechanism of action of the survival promoting properties of the p75NTR-derived peptide c29? (molecular biology, structural biology, biochemistry, cell biology)
- Can c29 modulate cognitive function to treat neurological disease (animal behavior, histology, electrophysiology)
- Matusica, D., Alfonsi, F., Turner, B. J., Butler, T. J., Shepheard, S. R., Rogers, M. L., Skeldal, S., Underwood, CK., Mangelsdorf, M & Coulson, E. J. (2016). Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment. J Cell Sci, 129(3), 517-530.
- Kerbler, G. M., Nedelska, Z., Fripp, J., Laczo, J., Vyhnalek, M., Lisy, J., Hamlin, AS., Rose, S., Hort J. & Coulson, E. J. (2015). Basal Forebrain Atrophy Contributes to Allocentric Navigation Impairment in Alzheimer's Disease Patients. Front Aging Neurosci, 7, 185.
- Kerbler, G. M., Fripp, J., Rowe, C. C., Villemagne, V. L., Salvado, O., Rose, S. & Coulson, EJ. Alzheimer's Disease Neuroimaging, I. (2015). Basal forebrain atrophy correlates with amyloid beta burden in Alzheimer's disease. Neuroimage Clin, 7, 105-113.
- Coulson, E. J., & Andersen, O. M. (2015). The A-B-C for SORting APP. J Neurochem, 135(1), 1-3.
- Matusica, D., & Coulson, E. J. (2014). Local versus long-range neurotrophin receptor signalling: endosomes are not just carriers for axonal transport. Semin Cell Dev Biol, 31, 57-63.
- Hort, J., Andel, R., Mokrisova, I., Gazova, I., Amlerova, J., Valis, M., Coulson EJ, Harrison J, Windisch M. & Laczo, J. (2014). Effect of donepezil in Alzheimer disease can be measured by a computerized human analog of the Morris water maze. Neurodegener Dis, 13(2-3), 192-196.
- Harper, C. B., Bademosi, A. T., Coulson, E. J., & Meunier, F. A. (2014). A role for SNAREs in neuronal survival? J Neurochem, 129(5), 753-755.
- Edwards, S. R., Hamlin, A. S., Marks, N., Coulson, E. J., & Smith, M. T. (2014). Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease. Clin Exp Pharmacol Physiol, 41(10), 798-806. doi: 10.1111/1440-1681.12277
- Boskovic, Z., Alfonsi, F., Rumballe, B. A., Fonseka, S., Windels, F., & Coulson, E. J. (2014). The role of p75NTR in cholinergic basal forebrain structure and function. J Neurosci, 34(39), 13033-13038. doi: 10.1523/JNEUROSCI.2364-14.2014
- D Matusica, S Skeldal, AM Sykes, N Palstra, A Sharma, EJ Coulson (2013) An intracellular domain fragment of the p75 neurotrophin receptor enhances TrkA receptor function. Journal of Biological Chemistry 288:11144-54.
- S Martin, CB Harper, LM May, EJ Coulson, FA Meunier, SL Osborne. (2013) Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death. PLoS ONE 8: e60152.
- R Ghaia, A Bugarcica, H Liub, SJ Norwooda, SS-C Lib, S Skeldal, EJ Coulson, RD Teasdale and BM Collins (2013) Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins. Proceedings of the National Academy of Sciences USA 110 (8) E643–E652
- AS Hamlin, F Windels, Z Boskovic, P Sah, EJ Coulson (2013) Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation. Plos One 8:e53472
- GM Kerbler, AS Hamlin, K Pannek, ND Kurniawan, MD Keller, SE Rose, EJ Coulson (2012) Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model NeuroImage 66: 133-141
- AM Sykes, N Palstra, D Abankwa, JM Hill, S Skeldal, D Matusica, P Venkatraman, JF Hancock, EJ Coulson (2012) The effects of transmembrane sequence and dimerization on cleavage of the p75 neurotrophin receptor by g-secretase. Journal of Biological Chemistry 287:43810-43824
- S Skeldal, AM Sykes, S Glerup, D Matusica, N Palstra, H Autio, Z Boskovic, P Madsen, E Castren, A Nykjaer, EJ Coulson (2012) Mapping of the interaction site between sortilin and the p75 neurotrophin receptor reveals a regulatory role for the sortilin intracellular domain in p75 neurotrophin receptor shedding and apoptosis. Journal of Biological Chemistry 287:43758-43809
- S Skeldal, D Matusica, A Nykjaer, EJ Coulson (2011) Proteolytic processing of the p75 neurotrophin receptor: a prerequisite for signaling? Bioessays 33:614-662.
- PR Dodd, EJ Coulson (2011) Post-synaptic Scaffolding Protein Interactions with Glutamate Receptors in Synaptic Dysfunction and Alzheimer's Disease. Progress in Neurobiology 93(4):509-21
- DT Proctor, EJ Coulson, PR Dodd (2010) Reduction in post-synaptic scaffolding PSD-95 and SAP-102 protein levels in the Alzheimer inferior temporal cortex is correlated with disease pathology. Journal of Alzheimer’s Disease 21(3):795-811
- MJ Colditz, VS Catts, NAl-Menhali, G Osborne PF Bartlett, EJ Coulson (2010) p75 neurotrophin receptor regulates basal and fluoxetine-stimulated hippocampal neurogenesis. Experimental Brain Research 200:161-7 (selected to be printed in the 200th issue)
- EJ Coulson, LM May, AM Sykes, AS Hamlin (2009) The role of the p75 neurotrophin receptor in cholinergic dysfunction in Alzheimer’s disease. The Neuroscientist 15:317-23
- A Sotthibundhu, QX Li, W Thangnipon, EJ Coulson (2009) Aβ1–42 stimulates adult SVZ neurogenesis through the p75 neurotrophin receptor. Neurobiology of Aging 30:1975-1985
- VS Catts, N Al-Menhali, THJ Burne, MJ Colditz, EJ Coulson (2008) The p75 neurotrophin receptor regulates hippocampal neurogenesis and related behaviours. European Journal of Neuroscience 28:883-92
- CK Underwood, EJ Coulson (2008) Molecules in Focus: p75 neurotrophin receptor. International Journal of Biochemistry and Cell Biology 40: 1664-68.
- A Sotthibundhu, AM Sykes, B Fox, CK Underwood, W Thangnipon, EJ Coulson (2008) β-amyloid1-42 induces neuronal death through the p75 neurotrophin receptor C-terminal fragment. Journal of Neuroscience 28: 3941-46
- EJ Coulson, LM May, SL Osborne, K Reid, CK Underwood, F Meunier, PF Bartlett, P Sah (2008) p75 neurotrophin receptor mediates neuronal cell death by activating GIRK channels through phosphatidylinositol 4,5-bisphosphate. Journal of Neuroscience 28: 315-24.
- CK Underwood, K Reid, LM May, PF Bartlett, EJ Coulson (2008) Palmitoylation of the C-terminal fragment of p75NTR regulates death signaling and is required for subsequent cleavage by γ-secretase. Molecular and Cellular Neuroscience 37: 346-58
- KM Young, T Merson, A Sotthibundhu, EJ Coulson, PF Bartlett (2007). p75NTR expression defines a population of BDNF-responsive neurogenic precursor cells. Journal of Neuroscience 27:5146-55
- EJ Coulson. (2006) Does the p75 neurotrophin receptor mediate Aβ-induced toxicity in Alzheimer’s disease? Journal of Neurochemistry 98:654-60
- EJ Coulson, K Reid, K Shipham, S Morley, TJ Kilpatrick, PF Bartlett. (2004) The role of neurotransmission and the Chopper domain in p75NTR death signaling. Progress in Brain Research 143:41-62
- EJ Coulson, K Reid, M Baca, K A Shiphan, S M Hulett, TJ Kilpatrick, PF Bartlett (2000) Chopper, a new death domain of the p75 neurotrophin receptor which mediates rapid neuronal cell death. Journal of Biological Chemistry 275:30537-45
- EJ Coulson, K Reid, GL Barrett, PF Bartlett (1999) p75NTR-mediated neuronal death is promoted by Bcl-2 and protected by BclxL. Journal of Biological Chemistry, 274:16387-91