Unveiling The Origin Of Munc18-1 And Alpha-synuclein Co-aggregation At Nanoscale
Funder
National Health and Medical Research Council
Funding Amount
$620,005.00
Summary
Our recent work on Munc18-1 mutations leading to a severe form of human early infantile epileptic encephalopathy (EIEE) led us to uncover a critical role for Munc18-1 in controlling the formation of toxic protein aggregates containing ?-Synuclein. Targeting the Munc18-1 ?-Synuclein interaction may have therapeutic values not only for EIEE but also for other neurological diseases characterised by protein aggregations.
Investigation Into The Intervention Of Arterial Thrombosis And Atherosclerosis Using Shear Sensitive Nanoparticle Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$462,601.00
Summary
In this project we aim to provide a targeted therapy that inhibits atherosclerosis, in-stent restenosis and thrombosis; pathologies characterized by high shear stress due to a reduction in the vessel lumen. We will apply microfluidic technology to characterize lipid nano-capsules that are tagged with antibodies against activated platelets or VCAM-1, loaded with anti-platelet or immune suppressive drugs and are prone to rupture specifically under high shear stress conditions.
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.
Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
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.
Regulation Of Receptors That Control Platelet Function Under Shear Stress
Funder
National Health and Medical Research Council
Funding Amount
$507,273.00
Summary
Specialized human blood cells that control blood loss and clotting (platelets) are currently difficult to test in the clinical laboratory, meaning patients are at risk of excessive bleeding or serious clot formation during disease or treatment. The aim of this proposal is to use our new reagents and assays to develop more reliable methods for evaluating relative bleeding or clotting risk in individuals.
Understanding The Function Of Recql4 In DNA Replication And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$698,447.00
Summary
We are interested in understanding how cancer forms. We are using information from human cancers to understand how a protein causes cancer. We are using models to understand how mutations in this protein give rise to bone cancer. These models are used together with detailed biochemistry to understand how the mutations affect protein function.
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.
Identifying The Missing Heritability Of Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$461,104.00
Summary
One of the strongest risk factors for the development of breast cancer is having a close relative with the disease. Some advances have been made in understanding the specific genetic factors that underlie this susceptibility but these known genetic factors only explain about a third of the overall familial effects. This research will utilise our prior research, international research resources, new technology and supercomputing to identify the majority of genetic factors associated with breast c ....One of the strongest risk factors for the development of breast cancer is having a close relative with the disease. Some advances have been made in understanding the specific genetic factors that underlie this susceptibility but these known genetic factors only explain about a third of the overall familial effects. This research will utilise our prior research, international research resources, new technology and supercomputing to identify the majority of genetic factors associated with breast cancer susceptibility.Read moreRead less