Neurodegeneration Laboratory

L to R: Dr Tim Aumann and Dr Rogan Tinsley are search for ways to treat and diagnose Parkinson's disease.
L to R: Dr Tim Aumann and Dr Rogan Tinsley are search for ways to treat and diagnose Parkinson's disease.

Group Leader

Professor Malcolm Horne BMedSci MBBS PhD FRACP

Contact Details

Email:        malcolm.horne@florey.edu.au

Number of

Staff:        8 (4 Senior Research Officers/Research Officers and 4 Research Assistants)

Students:  7 (4 PhD and 3 Honours)

  • Adam Walker
  • Chathurini Fernadez
  • Christine Matthews
  • Chris Bye
  • Kate Egan
  • Krikor
  • Charlene Goodman

Research Interests

Current Projects

A number of neurodegenerative disorders are characterised by abnormal aggregation of protein in the cell and associated disturbance of synaptic function. In the case of Parkinson’s disease (PD) the relevant molecule is α-synuclein and a leading hypothesis is that dopamine itself contributes to this aggregation and thus to the genesis of PD. We have developed a mouse that models some of the events that lead to α-synuclein aggregation and our current studies are directed at exploiting this model.

In the case of motor neuron disease, SOD-1 is the offending protein. In work carried out this year, our team, led by Dr Julie Atkin, has shown that accumulation of SOD-1 results from a secretary failure and that protein disulphide isomerase plays an important role in ameliorating this effect. It appears that secretion of SOD-1 may play a part in normal cell life but also in causing disease. It also appears that α-synuclein may be secreted and we are examining the potential to examine this as a biomarker as well as a partner in causing disease. This work is led by Dr Rogan Tinsley. Current work is directed at understanding how these aggregations occur and cause cell damage. This is collaboration with Prof Phillip Nagley at Monash University.

Changes in axonal arbour of dopamine cells also occurs after nigral injury and this seems to provide a milieu that induces the dopamine phenotype and causes axonal sprouting – precisely the environment for implantation of stem cells. We have implanted whole embryo derived neurospheres into the nigra after depletion of dopamine cells and found that this induces new dopamine cells of host origin. We are now working to identify the source of these cells, as well as the chemical factors that lead to induction of these new cells. We have also shown that in the adult brain, there are cells capable of replacing dopamine cells lost by injury and these cells participate in brain repair. We have also developed single cell PCR, in conjunction with slice electrophysiology to show that there are cells resident in the nigra that can transform into dopamine cells and re-innervate the striatum. This work is led by Dr Tim Aumann.

We are also examining how changes in newly developed synapses in the nigrostriatal system and in the thalamocortical system control normal and abnormal learning. The development of new synapses in normal behaviour is a project led by Dr Aumman, whereas abnormal learning as a cause of dyskinesia is led by Dr Joohyung Lee.

Clinical studies related to PD are being performed. One study is a collaboration with Dr Justin Rubio of the HFI. In this study we are examining the genes of people with PD in Victoria and Tasmanian and are developing a gene chip to study how activity genes known to be involved in PD can influence the risk of the disease. In another pilot study we are examining the effect of exercise on PD. Exercise increases levels of Neurotrophic factors such as Glial Derived Neurotrophic Factor (GDNF) in the brain and has been shown to be effective in treating depression, presumably by increasing the levels of these factors. GDNF is effective in PD and thus exercise may also slow the related of PD by increasing the levels of these factors. We are also developing a device for measuring the various fluctuations in PD symptoms.

In collaboration with Dr John Forsythe, at Monash University, we are examining the use of biomaterials to create scaffolds on which to optimally grow nigral and striatal cells.

Laboratory Techniques

Funding

Research