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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.
Counteracting Age-associated Neurodegenerative Diseases Using Chaperone-based Amyloid Disaggregases
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In neurodegenerative diseases such as Alzheimer’s disease, proteins form clumps through changes in structure due to mutations or proteotoxic chemical insults. The formation of these toxic clumps causes brain cells to die prematurely triggering symptoms such as dementia. I have identified a molecular machine in human cells that efficiently clears these clumps. We are now developing strategies to activate this machine to repair damaged brain cells to slow/reserve neurodegenerative diseases.
Modulating Heat Shock Protein Expression In Skeletal Muscle To Improve The Pathophysiology Of Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$502,361.00
Summary
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy. Dystrophic muscles are fragile, prone to injury, and regenerate poorly after damage. Defective calcium handling has been implicated in these processes. We have revealed that upregulating levels of stress proteins called _heat shock proteins� (HSPs) can improve calcium regulation in muscular dystrophy. Modulating the HSP response has significant potential to delay the onset or slow the progression of DMD.