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
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.
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
Many bacterial pathogens invade host cells to replicate and avoid detection by the host. These pathogens interact with the host and by manipulating it to its benefit they establish an environment to survive in. A detailed understanding of the targeted hosts pathways and which are essential for pathogen survival is knowledge that will allow future development of therapeutic intervention strategies.
Regulated Intracellular Trafficking Of A Potassium Channel In Gastric Acid-secreting Cells
Funder
National Health and Medical Research Council
Funding Amount
$609,511.00
Summary
The cells of our bodies possess proteins that transport salts and other chemicals. These transport proteins must be correctly positioned in cells, a process that is poorly understood. If transport proteins are not positioned properly then diseases such as heart attack or diabetes may occur. Influencing the position of transport proteins may also be used to treat disease. This work investigates how a transport protein that shuttles potassium is correctly positioned in cells of the stomach.
MOLECULAR CELL BIOLOGICAL ANALYSIS OF CAVEOLIN SECRETION
Funder
National Health and Medical Research Council
Funding Amount
$536,657.00
Summary
Aggressive forms of prostate cancer are associated with the release of a protein, called caveolin, from the cancerous cells. Caveolin is normally embedded in the cell surface and drives the formation of microscopic pits termed caveolae. In this proposal we will investigate how caveolin is secreted with a long-term goal of preventing the secretion, or the action, of caveolin.
A Signalling Endosomal Network In T Cell Activation
Funder
National Health and Medical Research Council
Funding Amount
$428,016.00
Summary
T lymphocytes play a central role in the adaptive immune response, which specifically targets pathogens and cancer cells and creates the immunological memory. Activation of sometimes as little as one single receptor on a T cell triggers a cellular signal that rapidly expands and branches out in a multitude of sub-signals. Here we will use a combination of novel microscopy approaches to visualise how a network of dedicated intracellular compartments is in charge of these processes.
Molecular Characterisation Of Transverse Tubule Development In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$951,321.00
Summary
Muscle fibres contain an elaborate system of membranes that allow the fibre to contract. This proposal aims to understand how this membrane system develops and how this process is disrupted in disease.
Molecular Characterisation Of Clathrin-independent Endocytosis In Migrating Cells
Funder
National Health and Medical Research Council
Funding Amount
$870,495.00
Summary
Cell migration is an essential feature of physiological processes involved in embryo development, as well as disease conditions such as cancer metastasis. Cell movement requires extensive changes to the cell surface. We have identified a vital pathway involved in membrane trafficking during cell migration. This proposal aims to identify the cellular components involved in this pathway, screen for new inhibitors, and characterise the role of this pathway in migrating cancer cells.
Nuclear architecture is critical to the preservation of genome integrity. The aim of this research proposal is to delineate the role of chromatin organisation in transcription factor target search and damage site recruitment of DNA repair factor machinery. To achieve this I have developed fluorescence microscopy methods to monitor changes in chromatin structure with submicron resolution. Only with this technology can I determine how chromatin dynamics maintain genome integrity or induce disease.