Characterising The Beta-catenin Nuclear Targeting Pathway In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$485,081.00
Summary
Bowel cancer is caused by inherited gene mutations that cause build-up of beta-catenin protein in the cell nucleus. Bowel cancer is the second largest cause of cancer deaths in Australia. We aim to study the mechanisms controlling beta-catenin accumulation in the nucleus. We will characterise new signalling pathways that control movement and activity of beta-catenin in the nucleus. This will yield insights into the role of beta-catenin in cancer and possible targets for therapy.
Subcellular Trafficking Of P Proteins Of Human Pathogenic Viruses: Roles In Viral Pathogenicity And Targeting For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destructi ....In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destruction by the human immune system.Read moreRead less
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.
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.
The Role Of Protein Glycosylation In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$644,428.00
Summary
The parasites that cause malaria have unique proteins on their surface that are essential for infection of humans. These proteins are useful for making vaccines to train our immune system to recognize and block infection by the malaria parasite. Our latest research has shown that these proteins are modified with sugars that enhance parasite virulence. We are studying these modifications more closely to facilitate the development of improved malaria vaccines.
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.
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.
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less