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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.
Unraveling The Molecular Mechanism Of Tau Spread In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,252,244.00
Summary
Disease progression in Alzheimer's disease is still poorly understood. The project is based on new findings by the research team that suggest that core cellular pathways and building blocks of nerve cell connections are required to allow the spread of pathology in the brain. This project will establish whether these pathways can be used as effective targets to intercept disease progression and prevent further cognitive decline in Alzheimer's disease pathology.
Characterization Of The FHL Protein Family In Striated Muscle
Funder
National Health and Medical Research Council
Funding Amount
$500,750.00
Summary
This grant examines the role of a family of muscle proteins, called FHL proteins, in skeletal and heart muscle. Inherited muscular disorders such as muscular dystrophy and myopathies, cause muscle weakness, which may be profound and lead to premature death due to respiratory muscle failure, or cause mild weakness later in life. The proteins which are defective in these muscular dystrophies are structural muscle proteins, which link and stabilize the contractile fibres in muscle and protect the m ....This grant examines the role of a family of muscle proteins, called FHL proteins, in skeletal and heart muscle. Inherited muscular disorders such as muscular dystrophy and myopathies, cause muscle weakness, which may be profound and lead to premature death due to respiratory muscle failure, or cause mild weakness later in life. The proteins which are defective in these muscular dystrophies are structural muscle proteins, which link and stabilize the contractile fibres in muscle and protect the muscle from the stresses and damage resulting from repeated muscular contraction. We have identified that the FHL proteins, which are the focus of this grant application, bind to and potentially regulate muscle proteins, which have been shown to cause forms of muscular dystrophy and cardiomyopathy. Examination of these interactions will provide insights into the biological mechanism of these muscle disorders. Furthermore, one of these proteins, FHL1 is significantly increased in hypertrophic cardiomyopathy, heart muscle thickening, a major cause of sudden cardiac death in young adults. We are creating transgenic mice, which make increased levels of FHL1 protein in their heart muscle, to determine whether increased FHL1, by itself is sufficient to promote heart muscle thickening. These studies should lead to further understanding of the development of diseases of heart and skeletal muscle, which may lead to novel treatments in the future.Read moreRead less
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
Understanding The Cause Of Muscle Weakness In Nemaline Myopathy (NM) – Moving Towards The Development Of Targeted Treatments
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Congenital myopathy patients have unremitting, life-long muscle weakness that severely affects their quality of life and ability to perform normal daily activities. Currently no effective therapies exist for these conditions, largely due to our limited understanding of the mechanisms leading to muscle weakness. This ECF aims to determine the cause of weakness and test two therapies which have shown promise for other conditions and can be translated into clinical use for myopathies if effective.
Dissecting The Molecular Basis For Cell Movement And Midgut Colonisation In The Insect Stage Parasite - The Ookinete
Funder
National Health and Medical Research Council
Funding Amount
$48,365.00
Summary
Malaria parasites are a leading cause of infant mortality. Despite their global impact, no vaccine exists to prevent malaria disease and resistance to current drugs is prevalent. Cell movement is an essential process for parasite development yet its potential as a drug target remains unexplored. I seek to shed light on the molecular mechanisms underlying movement, focused on the motile insect stages. Understanding gained here will support the broader goal to identify targets for transmission-blo ....Malaria parasites are a leading cause of infant mortality. Despite their global impact, no vaccine exists to prevent malaria disease and resistance to current drugs is prevalent. Cell movement is an essential process for parasite development yet its potential as a drug target remains unexplored. I seek to shed light on the molecular mechanisms underlying movement, focused on the motile insect stages. Understanding gained here will support the broader goal to identify targets for transmission-blocking development.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