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.
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.
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
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.
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.
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.
Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
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.
Understanding How Membrane Trafficking Controls The Levels Of Alzheimer's Disease Causing A? Peptides
Funder
National Health and Medical Research Council
Funding Amount
$478,905.00
Summary
Alzheimer’s disease is a progressive neurological disorder and is the most common cause of dementia. No effective treatments are currently available. The toxic amyloid peptide 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.