The Role Of Clusterin In Preventing Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$352,662.00
Summary
In atherosclerosis, plaques are formed when damaged low density lipoprotein (LDL) and fibrinogen are deposited inside blood vessels. Clusterin is a protein that stabilises damaged clients in soluble complexes, thus preventing their deposition. This project will investigate the ability of clusterin to prevent the deposition of damaged LDL and fibrinogen. Elucidation of mechanisms for preventing protein deposition will identify novel therapeutic targets for the treatment of atherosclerosis.
I am a protein crystallographer determining the structures of medically important proteins such as proteases. I am also a bioinformatician leading the development of informatics systems for automated highthroughput crystallography, and bioinformatic analy
ER Stress-Unfolded Protein Response A Critical Metabolic Pathway For Airway Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$789,475.00
Summary
Airway remodelling in asthma is associated with poor clinical outcomes and is not prevented by current treatments. We have found endoplasmic reticulum stress (ERS) and associated unfolded protein response (UPR), a crucial process involve in cellular protein folding, play a key role in airway remodelling in asthma. This study will investigate whether inhibition of ERS prevents goblet cell metaplasia, mucus hypersecretion and fibrosis and can be used as a therapeutic strategy for severe asthma.
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.
My research is aimed at understanding how the structure and dynamics of proteins dictates their function. I use X-ray crystallography to determine the shapes of proteins. Proteins are not static, however - they move in complicated ways, and often their motion is critical to their function (molecular motors, for example). It is very difficult to 'watch' this movement in the lab, so I use computer simulation to try to understand how proteins move.
Skeletal Disease In A Dish: Using Novel In Vitro Disease Models Produced From Patient Induced Pluripotent Stem Cells To Reveal Pathogenic Mechanisms And Explore Treatments For Genetic Skeletal Disorders
Funder
National Health and Medical Research Council
Funding Amount
$808,551.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and a new in vitro cell reprogramming technology to induce them to form cartilage and bone cells to produce mutation-specific “disease in a dish” models. These models will allow us to answer questions about how specific mutations cause disease and test novel drug therapies