Northcott Neuroscience Laboratory Projects

Zebrafish models of Machado Joseph Disease

A Laird, K Yuan, N Mackovski, G Nicholson
In collaboration with Prof Tom Becker and the Developmental Neurobiology laboratory at the Brain and Mind Research Institute

Machado Joseph Disease (MJD, or spinocerebellar ataxia-3) is a fatal neurodegenerative disease that causes a lack of coordination and paralysis, leading to confinement to a wheelchair and high dependence care. MJD affects people of all ages and is particularly common in Indigenous communities of Arnhem Land in the Northern Territory. We have developed the first zebrafish model of MJD to allow us to study the causes of the disease and test potential drug treatments. Zebrafish, are well suited for use in these studies because they are transparent during development, allowing observation of disease neuroanatomy and pathology in the living animal and they can be treated with potential drugs through simple addition to the water they live in. Our zebrafish carry either the healthy or MJD-causing version of the human ataxin-3 protein. Using an automated movement tracking system we are able to track the swimming movement of our fish over time and also compare the effect of drug treatments on this movement.


Future students

We welcome future Honours, Masters and PhD students to contact us if they are interested in discussing projects available within our laboratory. (Email: angela.laird@sydney.edu.au)


Zebrafish Models

Although the cause of polyglutamine diseases is the known genetic abnormality, treatments to prevent or cure the disease have not yet been identified. We are using zebrafish models of spinocerebellar ataxia, including SCA-3 and SCA-6, to study disease mechanisms and trial potential drug therapies. Zebrafish are unique as they are the only vertebrate model where disease pathology can be seen in real time, due to their transparency during development. We have genetically modified zebrafish to express the mutated ATXN3 gene and we are currently observing the fish for signs of neurological dysfunction. To study the phenotypes expressed in our zebrafish we are employing neuroanatomical, biochemical and behavioural tools, including usage of a state-of-the-art behaviour tracking system. Following the characterisation of the disease features expressed by the fish we will commence screening drug treatments, aiming to reverse signs of the disease.