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.
Unraveling The Dynamic Munc18a:Syntaxin1 Interaction Required For Neurotransmission
Funder
National Health and Medical Research Council
Funding Amount
$674,591.00
Summary
Membrane trafficking, the topic of the 2013 Nobel prize in Medicine, is required for delivery of cellular cargo. This research will investigate the interactions and structures of proteins from the neuronal membrane trafficking system. Understanding how this system operates will expand our knowledge of processes fundamental to learning and memory and may ultimately lead to development of selective therapeutics for treating a range of diseases.
Molecular Dissection Of The Munc18c:Syntaxin4 Complex Required For Insulin-regulated Exocytosis In Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$601,008.00
Summary
When blood glucose levels are high, insulin signals to fat and muscle cells to remove glucose from the blood. The uptake of glucose relies on membrane fusion events that deliver a specific glucose transporter protein to the cell surface in response to insulin signals. This process is affected in Type II diabetes. Our research will characterise the regulation of these membrane fusion events and will be important for understanding how insulin signals are communicated in health and disease.
This research program aims to gain a detailed understanding of the organisation of the cell surface at the molecular level. The cell surface is organised into domains with distinct functions. Visualisation of these domains, identifying their important components, and understanding how they form and function will have huge importance for therapeutic strategies aimed at combatting the changes associated with cell transformation in cancer and in other human diseases such as muscular dystrophy.
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.
Prof Parton is a cell biologist studying how the plasma membrane functions in health and in disease. These studies have provided new insights into potential vehicles that can be used to introduce therapeutic agents into cells.
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.