Crouch Laboratory
| Contact: | Dr Peter Crouch |
|---|---|
| Phone: | +61 3 8344 4292 |
| Fax: | +61 3 8344 4004 |
| Email: | pjcrouch@unimelb.edu.au |
The research focus of the Crouch laboratory is neurodegenerative disease. Neurodegenerative disease involves progressive loss of function of the neuronal cells needed for our ability to think, move, breathe and swallow, and the most common forms include Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and motor neuron disease. Because the likelihood of developing neurodegenerative disease increases with increasing age, an ageing global population and an increasing life expectancy means that the incidence of neurodegenerative disease is escalating at an unprecedented rate. An unfortunate commonality shared by all neurodegenerative diseases is that effective therapeutics do not exist. The ultimate objective of the Crouch laboratory is to complete research that will expedite the development of effective therapeutics. To achieve this we undertake research in two key research areas; the testing of potential new therapeutics and the examination of impaired energy metabolism in neuronal failure.
Key Research Areas
Testing of potential new therapeutics.
Working in close collaboration with chemists and biotechnology companies provides the Crouch laboratory with a unique opportunity to conduct pre-clinical studies using compounds under development as potential therapeutics for neurodegenerative disease. These studies are conducted using in vitro and in vivo models of neurodegenerative disease. The aim of these studies is to generate information on the mechanism of action for these compounds and to identify compounds that have the best potential to proceed further towards clinical testing.
Impaired energy metabolism in neuronal failure.
A major obstacle in the development of therapeutics to treat neurodegenerative disease is that the cellular causes of neuronal failure in these diseases are incompletely understood. An important part of our research therefore focuses on trying to define the processes that lead to neuronal failure. Neurons are the most energy hungry cells in the human body and a relatively small impediment to their ability to generate energy can have large effect on neuronal activity. By using a range of cell culture models the aim of our research in this area of work is to examine the effects of impaired energy metabolism on cellular functions relative to neuronal activity.
Objectives
Major Achievements
Techniques
- Animal models of neurodegenerative disease
- Cognitive and locomotor testing of animals
- Cell culture
- Western blot
- Immunocytochemistry
- Enzyme activity assays
- Cell energy metabolism
Collaborations
National:
- Dr Anthony White, Department of Pathology, University of Melbourne
- Assoc. Prof. Kevin Barnham, Department of Pathology, University of Melbourne
- Dr Paul Donnelly, School of Chemistry, University of Melbourne
- Assoc. Prof. Robert Cherny, Prana Biotechnology
- Prof. Ashley Bush, Mental Health Research Institute
- Prof. Colin Masters, Mental Health Research Institute
- Assoc. Prof. Anthony Hannan, Florey Neuroscience Institutes
- Assoc. Prof. Ian Trounce, Centre for Eye Research Australia
International:
- Prof. James Shen, Academia Sinica, Taiwan
Funding
- National Health and Medical Research Council (2009-2013)
- Bethlehem Griffiths Research Foundation (2006, 2010-2011)
- Brain Foundation (2011)
- Motor Neuron Disease Research Institute of Australia (2008, 2010-2011)
- ANZ Charitable Trusts (Judith Jane Mason & Harold Stannett Williams Memorial Foundation) (2011)
- Melbourne Neuroscience Institute (2011)
- University of Melbourne (2007)
- CASS Foundation (2009, 2010)
Recent Publications
- Crouch PJ, Blake R, Duce JA, Ciccotosto GD, Li Q-X, Barnham KJ, Curtain CC, Cherny RA, Cappai R, Dyrks T, Masters CL, Trounce IA. 2005. Copper-dependant inhibition of human cytochrome c oxidase by a dimeric conformer of Aβ1-42. Journal of Neuroscience 25:672-679.
- Crouch PJ, Barnham KJ, Duce, JA, Blake RE, Masters CL, Trounce IA. 2006. Copper-dependent inhibition of cytochrome c oxidase by Aβ1-42 requires reduced methionine at residue 35 of the Aβ peptide. Journal of Neurochemistry 99:226-236.
- Crouch PJ, Harding S-ME, White AR, Camakaris J, Bush AI, Masters CL. 2008. Mechanisms of Aβ mediated neurodegeneration in Alzheimer’s disease. The International Journal of Biochemistry and Cell Biology 40(2):181-198.
- Crouch PJ, Hung LW, Adlard PA, Cortes M, Lal V, Filiz G, Perez KA, Nurjono M, Caragounis A, Du T, Laughton K, Volitakis I, Bush AI, Li QX, Masters CL, Cappai R, Cherny, RA, Donnelly PS, White AR, Branham KJ. 2009. Increasing Cu bioavailability inhibits Aβ oligomers and tau phosphorylation. Proceedings of the National Academy of Sciences USA 106(2):381-386.
- Crouch PJ, Tew DJ, Du T, Nguyen DN, Caragounis A, Filiz G, Blake RE, Trounce IA, Soon CPW, Laughton K, Perez KA, Li QX, Cherny RA, Masters CL, Barnham KJ, White AR. 2009. Restored degradation of the Alzheimer’s amyloid-β peptide by targeting amyloid formation. Journal of Neurochemistry 108:1198-1207.
- Adlard PA, Bica L, White AR, Cappai R, Nurjuno M, Crouch PJ, Filiz G, Finkelstein DI, Bush AI. 2011. Metal ionophore treatment restores synaptic plasticity in a mouse model of Alzheimer’s disease. PLoS ONE. 6(3):e17669.
- Crouch PJ, Savva MS, Hung LW, Donnelly PS, Mot AI, Parker SJ, Greenough MA, Volitakis I, Adlard PA, Cherny RA, Masters CL, Bush AI, Barnham KJ, White AR. 2011.