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.
Blood clotting is the underlying cause of heart attacks and strokes. We have discovered that the protein, ERp5, is essential for normal blood clotting. Our preliminary findings indicate that ERp5 controls the function of blood platelets in clotting. Our overall aim is to elucidate how ERp5 regulates platelet function. It is crucial that we understand how ERp5 functions in blood clotting if we are to effectively target it in disease.
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.
Characterisation Of TIA Proteins In RNA Recognition And Stress Granule Formation
Funder
National Health and Medical Research Council
Funding Amount
$566,966.00
Summary
Cells in our body need to be able to respond to stresses such as heat, hypoxia, chemical stress or infection. In this project we investigate the specialized TIA proteins that have the job of protecting RNA in stressed cells. We will investigate the way TIA proteins recognize particular mRNA and form temporary protective clusters. By better understanding this process we will gain insight into the way in which cells are susceptible to damage in diseases including neurodegenerative disease.
PYROXD1 - A Novel Myopathy Disease Gene Identifies A Redox Pathway Essential For Life
Funder
National Health and Medical Research Council
Funding Amount
$1,247,992.00
Summary
An Australian family with a rare myopathy has led to the discovery of a new gene called PYROXD1; a gene that all cells need to survive. PYROXD1 plays a critical role in protecting cells from oxidative stress. We are using patient samples and mouse models to find out what PYROXD1 does that is vital for cell and animal life. We will test whether redox therapies developed for neurodegenerative disorders might help patients with rare neuromuscular disorders, for whom there are no treatment options.
Most diseases are much more common in the elderly. The reasons are poorly understood. We have evidence that the most common eye diseases, cataract and presbyopia, are due to the fact that the large molecules that make up the lens do not turnover. In lenses of older people proteins, which make up the bulk of the transparent tissue, become degraded. It turns out that very long lived proteins are quite common in the body. This proposal seeks to determine what role degradation of these ancient prote ....Most diseases are much more common in the elderly. The reasons are poorly understood. We have evidence that the most common eye diseases, cataract and presbyopia, are due to the fact that the large molecules that make up the lens do not turnover. In lenses of older people proteins, which make up the bulk of the transparent tissue, become degraded. It turns out that very long lived proteins are quite common in the body. This proposal seeks to determine what role degradation of these ancient proteins has in other diseases of aging.Read moreRead less
Understanding Age-related Protein Aggregation. The Mechanism Of Cataract And Its Prevention
Funder
National Health and Medical Research Council
Funding Amount
$709,333.00
Summary
Cataract arises from clouding of the eye lens due to the aggregation of crystallin proteins whose high concentration and close packing facilitate lens transparency. This proposal will investigate crystallin structure and interactions to understand the reasons for cataract formation and its prevention via the design of aggregation inhibitors. The results will facilitate the development of drugs to prevent cataract and other related protein aggregation diseases, e.g. Alzheimer’s and Parkinson’s.
Characterisation Of The Pathogenesis Of FHL1 Myopathies
Funder
National Health and Medical Research Council
Funding Amount
$748,652.00
Summary
Skeletal muscle is the most abundant tissue in the body and dynamically capable of responding to many environmental stresses. A key cellular process that has developed in muscle to facilitate adaptive responses is autophagy, a mechanism that facilitates the degradation and recycling of cellular debris. Defects in autophagy cause muscle disease. In this study we will identify a novel gene that regulates autophagy and will investigate how mutations in this gene cause muscle disease.
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.