Role Of Hsp40 And Hsp70 In Huntingtin Misfolding, Oligomerization And Inclusion Assembly
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
Huntington disease results from a mutation that causes the Htt protein to become abnormally sticky and form toxic clusters in neurons. Cells have natural defences to clustering with proteins called chaperones, which are exciting therapeutic targets. This project will examine how chaperones defend against toxic Htt clustering with cutting-edge imaging technologies. The knowledge gained will aid in designing therapeutic strategies that stimulate the defence processes and suppress the clusters.
Pathogenic And Adaptive Molecular Interactions With Mutant Huntingtin Exon 1
Funder
National Health and Medical Research Council
Funding Amount
$727,117.00
Summary
This project aims to determine how the gene mutation that causes Huntington’s disease (HD) damages cells in the brain. The diseased gene creates a protein that is abnormally sticky, which causes it to form clumps. Our goal is to determine the components of the cell that are disrupted and damaged as clumping happens. Understanding this link will enable therapeutics to be logically designed in efforts to prevent harm to the brain, potentially before symptoms are evident.
Viewing The Cellular Responses In Huntington’s Disease Through An Aggreomics Framework
Funder
National Health and Medical Research Council
Funding Amount
$363,218.00
Summary
Huntington disease results from a mutation that causes the Htt protein to form abnormal toxic clusters in neurons that eventually leads to cell death. This project will develop and apply new technology to identify how the clustering process damages cells and will measure all the gene expression changes that occur during the clustering process. The project offers much potential for revealing new therapeutic targets to this incurable disease.
Studies On The Biochemistry And Molecular Biology Of Amyloidosis
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
Amyloidoses are a group of diseases in which protein is abnormally deposited in various organs of the body. The prototypic amyloidosis is Alzheimer's disease (AD), a dementia causing-illness in which a protein known as Abeta is deposited in the brain. The central aim of my research is to understand the molecular etiology of AD and other amyloidoses, with a view to identifying new targets for drug development.
Understanding The Role And Mechanism Of Interaction Of Small Heat-shock Proteins In Age-related Disease
Funder
National Health and Medical Research Council
Funding Amount
$270,827.00
Summary
Protein precipitation is associated with a diversity of age-related diseases such as cataract and Alzheimer's. Within cells, a group of chaperones called the small heat-shock proteins (sHSPs) function by binding to destabilized proteins, however, common in vivo modifications can disrupt their cellular role leading to co-aggregation in a number of age-related diseases. This study will use state of the art mass spectrometry to examine the mechanism by which sHSPs interact with client proteins.
Targeting Small Heat Shock Proteins In Diseases Associated With Alpha-synuclein Aggregation
Funder
National Health and Medical Research Council
Summary
This research will provide fundamental insight into processes that control the onset and progression of neurological diseases such as Parkinson’s disease, and may lead to the development of novel drugs to treat these disorders. The work will increase Australia's international research standing and provide high-quality multi-disciplinary training to research students.
Protein Homeostasis, Protein Aggregation And Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
There is a desperate need for biomarkers and therapeutics for Motor Neurone Disease (MND). Mutations in a growing list of genes are implicated as a cause of MND, although the way these cause MND remains a mystery. I aim to build a uniquely positioned research team that approaches this problem from a protein centric view and incorporating strategic collaborative efforts to the understanding of the pathogenesis of MND; the longterm goal of which is translation to biomarkers and therapeutics.