Membrane Attachment And Components Of The Ca2+ -triggered Release Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$386,498.00
Summary
Understanding and harnessing the fundamental cellular process of secretion will provide a wealth of new approaches to addressing problems associated with aging & disorders that are major health care burdens (e.g. neurodegeneration & diabetes). Understanding the vesicle docked state, and the contributions of different molecular components to the release process provides for unique insights into the underlying molecular mechanisms, thereby enabling safe, targeted control of this critical process.
Identification And Characterization Of Novel Proteins In Endosomal Cholesterol Transport
Funder
National Health and Medical Research Council
Funding Amount
$540,636.00
Summary
Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against hea ....Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against heart disease and dementia.Read moreRead less
Membrane Trafficking Of BACE1 And Amyloid Precursor Protein In Primary Neurons And The Production Of Abeta Amyloid Peptides
Funder
National Health and Medical Research Council
Funding Amount
$705,984.00
Summary
The development of Alzheimer’s disease results from the generation of toxic peptides by the cleavage of a membrane protein by an enzyme called BACE. A key feature of which regulates the generation of toxic peptides involves the movement of BACE between compartments in the cell by a process known as membrane transport. Our recent work has identified the itinerary of BACE in the cell. The studies here will reveal the molecular machinery of the BACE pathway in neurons. This fundamental informati
STRUCTURE, FUNCTION AND REGULATION OF F-TYPE ATP SYNTHASES
Funder
National Health and Medical Research Council
Funding Amount
$544,660.00
Summary
ATP synthase is the molecular machinery that converts energy derived from nutrients or photosynthesis into the universal biological energy carrier ATP (adenosine triphosphate). This is one of the most fundamental processes of life and is conserved from bacteria to plants to humans. Understanding how bacterial and mitochondrial ATP synthases work in molecular detail will have wide-ranging implications for both medicine (in understanding metabolic disorders, controlled cell death and aging) and th ....ATP synthase is the molecular machinery that converts energy derived from nutrients or photosynthesis into the universal biological energy carrier ATP (adenosine triphosphate). This is one of the most fundamental processes of life and is conserved from bacteria to plants to humans. Understanding how bacterial and mitochondrial ATP synthases work in molecular detail will have wide-ranging implications for both medicine (in understanding metabolic disorders, controlled cell death and aging) and the design of new antibacterial agents.Read moreRead less
Membrane Trafficking Of The ?-secretase, BACE1, And The Generation Of Alzheimer's Disease A? Amyloid Peptides
Funder
National Health and Medical Research Council
Funding Amount
$465,704.00
Summary
Alzheimer’s disease results from the production of toxic neuropeptides by the action of an enzyme called BACE. The generation of toxic peptides requires the movement or trafficking of BACE between different cell compartments. This research will reveal the molecular machinery of the BACE transport pathway. This new knowledge will provide a strategy to develop drugs to inhibit BACE activity and the production of the toxic peptide, which would be of significant benefit to patients and families.
Regulation Of Inflammation And Coagulation By Microparticles Containing SerpinB2
Funder
National Health and Medical Research Council
Funding Amount
$594,133.00
Summary
SerpinB2 is a protein that is abundant during many types of inflammation. However, what this protein actually does remains an enigma. We have found that SerpinB2 is associated with microparticles; small particles found in everyone’s blood, that are used by cells to communicate with each other. We believe inappropriate levels of SerpinB2 on these microparticles change both inflammation and blood clotting; a contention with implications for several diseases including pre-eclampsia and cancer.
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
Antibiotic resistant bacteria cause life-threatening diseases and represent a major public health problem. Globally, drug-resistant infections currently cause over 500,000 deaths annually and this figure is projected to exceed 10 million by 2050. Venom peptides are a new avenue of antibiotic discovery. This proposal aims to define how these peptides interact with the cellular power generator, ATP synthase, to provide a basis for exploiting their potential to treat bacterial infections.
Imaging The Machinery Of Bacterial Locomotion At Atomic Resolution
Funder
National Health and Medical Research Council
Funding Amount
$360,732.00
Summary
Our aim is to a) understand and b) sabotage the machinery of locomotion in bacteria. The flagellar motor propels bacteria at 100s of revolutions per second through viscous media making this the most powerful motor known to man. Bacteria can sense their environment and make informed decisions to avoid hazards or find food. Understanding how this machinery works in atomic detail is expected to have implications for both the development of new antibacterials and in the area of nano-medicine.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.