Mechanism Of Action Of Dynamin Ring Stabilizer Compounds Controlling The Actin Cytoskeleton
Funder
National Health and Medical Research Council
Funding Amount
$659,360.00
Summary
We will test our hypothesis that ring stabilizer (RS) compounds we invented may become future proteinuric kidney disease therapeutics. The global epidemic of kidney disease eludes present treatments. Dysfunction of podocyte cells accounts for 90% of end-stage kidney diseases. Our pilot data shows that our ring stabilizer compounds restore podocyte function in vitro and kidney function in animal models. We aim to understand their mechanism of action.
Dissecting The Molecular Basis Of Actin Filament Disassembly In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$576,716.00
Summary
Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug targe ....Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug target.Read moreRead less
Uncover How Myosin-6 Underpins The Ca2+-dependent Recruitment Of Secretory Vesicles To The Cortical Actin Network
Funder
National Health and Medical Research Council
Funding Amount
$559,295.00
Summary
Neuronal communication relies on the process of exocytosis by which neurons release a neurotransmitter. Exocytosis underpins processes such as the simplest muscle movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how the protein Myosin-6 controls exocytosis. This research will be important for understanding how neurons communicate in health and disease and will be relevant to other processes such as insulin release ....Neuronal communication relies on the process of exocytosis by which neurons release a neurotransmitter. Exocytosis underpins processes such as the simplest muscle movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how the protein Myosin-6 controls exocytosis. This research will be important for understanding how neurons communicate in health and disease and will be relevant to other processes such as insulin release in diabetes.Read moreRead less
Molecular Dissection Of The Actin Cytoskeleton In Exocytosis Using Intravital Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$1,206,869.00
Summary
The proteins actin and tropomyosin form networks in cells that are involved in all of the key processes that are hijacked when a cell becomes cancerous. We discovered that the tropomyosin is the key to the function of a network and have developed drugs that target the cancer-associated tropomyosin. We will examine how the drugs kill cancer cells using a novel method, developed by us, to visualize drug activity in real time, and validate their impact on the target filaments in living tissue.
Regulation Of Glucose Uptake By Tropomyosins And Myosins
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
Defective import of glucose from the blood into fat and muscle is a key cause of adult-onset diabetes. We have identified a novel mechanical structure within muscle and fat cells defined by the protein tropomyosin that is involved in glucose import and potentially provides new targets for treatment of adult-onset diabetes and obesity.
Targeting The Synaptic Actin Cytoskeleton In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$840,741.00
Summary
Dementias have become one of the fastest growing sources of major disease burdens in developed countries with about one in fifteen Australians older than 65 being affected. We will study how pathological stimuli disrupt nerve cell connections in the brain by impacting on the cellular architecture at these connections. Findings from our study will provide profound new insights in how nerve cells communicate with each other and how this communication is breaking down in disease.
Regulation Of ERK Driven Cell Proliferation By The Actin Cytoskeleton
Funder
National Health and Medical Research Council
Funding Amount
$920,972.00
Summary
The cells in your body respond to external signals and control their proliferation by transmitting signals from one part of the cell to another. This has usually been thought to involve the movement of signals through a liquid medium without the involvement of any machinery to control the movement. The project aims to test the role of the architecture of the cells in physically moving a growth signal from one place to another. We think that the architecture involved plays a key role in cancer.
The Role Of LIM Domain Kinase 1 In The Pathogenesis Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$565,531.00
Summary
Alzheimer’s disease is characterized by progressive loss of cognition. Few Australians have remained untouched by the effects of Alzheimer’s disease in their families or social circles. Unfortunately, there is no cure and current therapies are limited to modest symptomatic relief. This project will explore the role of a protein that regulates the structural integrity of brain cells in disease, and test if targeting this protein could prevent disease progression.
This proposal investigates processes that regulate the cell cytoskeleton to control shape and the dynamics membranes, with a view to developing a generic antiviral therapy. As viruses rely upon the cell cytoskeleton to initiate an infection, we posit that enzymes that control the cytoskeleton can be targeted to block infection.
(Dys)Regulating Junctional Tension: A Novel Mechanism In Tumor Cell Biology
Funder
National Health and Medical Research Council
Funding Amount
$732,391.00
Summary
This project will study how cancer cells are forced out of their original tissue of origin. This process, called oncogenic extrusion, is important to allow cancer cells to proliferate and invade their surrounding tissue. We have discovered a new cellular mechanism that causes oncogenic extrusion and aim to understand its molecular basis and test how it contributes to breast cancer.