Dissecting A Serial Killer: Investigating The Degranulation Pathways In Cytotoxic Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$604,459.00
Summary
When cells of the human body become cancerous or infected with virus, the body's immune system engages cytotoxic lymphocytes, known as "killer cells", that secrete an auxiliary of toxic proteins to eliminate these cells. The aim of this study is to investigate the mechanisms by which these critical immune cells accomplish this task. Importantly, humans who are genetically lacking in critical constituents of the cytotoxic lymphocyte are less able to fight off a viral infection and may be at a hig ....When cells of the human body become cancerous or infected with virus, the body's immune system engages cytotoxic lymphocytes, known as "killer cells", that secrete an auxiliary of toxic proteins to eliminate these cells. The aim of this study is to investigate the mechanisms by which these critical immune cells accomplish this task. Importantly, humans who are genetically lacking in critical constituents of the cytotoxic lymphocyte are less able to fight off a viral infection and may be at a higher risk of developing cancer.Read moreRead less
Dysferlinopathy: A Genetic Disease Sheds Light On Membrane Repair For Muscle And Cardiac Injury
Funder
National Health and Medical Research Council
Funding Amount
$782,806.00
Summary
Muscles are damaged all of the time, as we stretch and contract them, but we don't fully understand how they repair themselves. We are studying the molecular steps taken by a muscle cell to repair membrane damage. Our research will provide valuable insights into how to treat muscular dystrophy and other conditions characterised by membrane damage to cells, such as heart attack and stroke.
Neuronal communication relies on the process of exocytosis by which neurons release a neurotransmitter. Exocytosis is critical for 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 Munc18 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.
The Functional Interplay Between Alpha Synuclein And Synaptophysin In Synaptic Vesicle Recycling
Funder
National Health and Medical Research Council
Funding Amount
$405,461.00
Summary
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder, affecting 7 million people worldwide. ?-synuclein is a protein in that brain that is likely to contribute to the death of brain cells in PD, but the normal role of the protein remains unknown. This study will investigate the function of ?-synuclein in maintaining normal healthy brain activity. In addition, this work will help us understand the processes that go awry in neurodegenerative disease states such as PD.
Understanding The Cellular Processing Of Targeted Nanoparticles For Improved Therapeutic Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$625,477.00
Summary
Nanotechnology has the potential to transform the way we treat many diseases. This project will investigate how nanoengineered particles can be used to improve the effectiveness of vaccines. Nanoparticles can protect the delicate vaccine cargo from degradation, and will be targeted specifically to the cells in the body that most effectively induce the maximum theraputic response. This study will improve our understanding of how nanovaccines work and develop new ways of delivering vaccines.
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
Insulin triggers glucose uptake into fat and muscle tissue, a process that is defective in type 2 diabetes. Insulin does this by triggering a complex cascade of actions once it binds to muscle and fat cells. We will analyse the function of a crucial protein within this cascade. This protein is mutated in humans with severe insulin resistance and our proposed project will dissect how this protein works potentially providing a novel drug target to treat diabetes.
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.
How Do Small Extracellular Vesicles Contribute To The Development Of Prion Disease
Funder
National Health and Medical Research Council
Funding Amount
$563,897.00
Summary
Prion diseases are transmissible neurodegenerative disorders associated with the misfolding of the prion protein. This proposal will investigate how cells release the infectious agent responsible for prion diseases in small nanovesicles known as exosomes. We will characterise the novel processed forms of the proteins involved in these two neurodegenerative diseases within the exosomes and investigate whether the genetic content of exosomes has diagnostic potential.
Dysferlin And The Emergency Vesicle Fusion Of Membrane Repair
Funder
National Health and Medical Research Council
Funding Amount
$481,496.00
Summary
Membrane repair is a vital cell survival mechanism of all eukaryotic cells, using calcium-triggered vesicle fusion to ‘patch’ membrane ruptures. The muscular dystrophy protein dysferlin is a key mediator of membrane repair, although, exactly how dysferlin mends membranes has been unclear. We show that the calcium that floods through membrane tears, activates a group of enzymes called calpains, that specifically cleave dysferlin to release a specialist vesicle-fusion module for membrane repair.