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.
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.
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.
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.
I am a cell biologist investigating the means by which intracellular compartmentalization of signalling proteins determines signalling outcomes and cell fate. I focus particularly on signals that regulate immune function and cancer progression.
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.
Regulation Of The Nedd4 Family Of Ubiquitin Ligases By Adaptor And Accessory Proteins In Normal Physiology And In Disease
Funder
National Health and Medical Research Council
Funding Amount
$609,424.00
Summary
In part this proposal is to understand how the body controls iron uptake through iron transporters DMT1 and Nramp1. We will study the regulation of these transporters by proteins called Ndfip1, Ndfip2 and arrestins. We will also study the functions of these proteins in controlling ubiquitination, a fundamental process required for cellular homeostasis. The results from this study may ultimately contribute to the development of novel therapies for certain human diseases.
Regulation Of VEGFR Trafficking And Signal Transduction By The Ubiquitin Ligase Nedd4
Funder
National Health and Medical Research Council
Funding Amount
$388,347.00
Summary
Our recent work has discovered that the Nedd4 gene is crucial for the growth and development of blood vessels and lymphatic vessels. Our data suggest that Nedd4 controls vessel growth by regulating the levels and signalling activity of the key vascular growth factor receptors VEGFR-2 and VEGFR-3. The goals of this proposal are to define precisely how Nedd4-1 regulates the activity of these receptors and how VEGFR signalling could be better targeted to treat vascular disorders.
Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.