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.
The Preferential Release Of Young Insulin Secretory Granules.
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
The aim of this study is to investigate the cause of reduced glucose induced insulin secretion in type 2 diabetes. In pancreatic beta-cells, insulin is packaged and stored in secretory granules (SGs). Upon stimulation, these SGs deliver insulin to the bloodstream. It is known that insulin SGs exist in two functionally distinct pools; and one pool is preferentially secreted upon stimulation. How a cell can differentiate the two SG pools is unclear, and we will address this issue in this project.
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.
INHIBITORS OF DENGUE VIRUS NONSTRUCTURAL PROTEIN 5 NUCLEAR TRAFFICKING AS PROBES OF DENGUE BIOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$741,136.00
Summary
Viral disease is one of the most significant health problems world-wide, making the identification of new therapeutics of critical importance. We aim to characterise in detail novel compounds which inhibit the interaction of the host cell with Dengue virus, and test them in a series of relevant infectious models for Dengue.
Endosomal Sorting Of Amyloid Precursor Protein In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$858,643.00
Summary
Alzheimer's Disease is a progressive neurological disorder and is the most common cause of dementia. Effective treatments are desperately needed, but none are currently available. The toxic amyloid peptide A? is central to disease pathology and is derived from breakdown of the Alzheimer’s amyloid precursor protein (APP). In this project we will examine the interactions between APP and the molecular machinery that controls its location in the cell and subsequent degradation.
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.
Enhanced Nuclear Transport In Transformed Cells; Implications For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$628,650.00
Summary
We have found that cancer cells are different to normal cells in terms of their ability to accumulate molecules in the cell nucleus. We intend to pursue this observation in detail, to understand the mechanism thereof, and the extent to which all types of cancer cells are similar in this regard. The results will have high relevance to understanding of oncogenesis, and of utility in approaches to anti-cancer therapies relying on the delivery of nuclear acting drugs.
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.
The Role Of Intracellular Protein Trafficking In Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease (AD) is a progressive neurological disorder and is the most common cause of dementia. The development of therapies must be preceded by a thorough understanding of the molecular processes that underpin the disease. In this project we will examine the interactions between the Alzheimer’s precursor protein (APP) and the molecular machinery that controls its intracellular localization and breakdown to the toxic A? peptide that is central to disease pathology.
Sorting Out The Synapse: The Role Of Intracellular Trafficking In NMDA Receptor Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$631,966.00
Summary
When the normal levels of cell surface proteins in neurons are reduced this can lead to a variety of debilitating neurodegenerative and neuronal diseases. These levels are maintained by organelles inside the neuron called endosomes. In this project we will examine how cell surface receptors required for synapse formation are transported through endosomes by a protein machine called retromer, which is important in both Alzheimer’s and Parkinson’s disease.