Proteins form up to 25% of our diet. The first step in protein absorption is the digestion of protein into smaller units called peptides and amino acids. Both components are subsequently taken up by specialised cells in the wall of the intestine. In this project we plan to study how protein absorption occurs at the surface of these intestinal cells and investigate why this process fails in malabsorption syndromes, where the uptake of amino acids is impaired.
The proposed research project involves a fundamental biochemical and biophysical investigation of a protein (ABCA4) intimately involved in the visual process. The precise role of ABCA4 in vision has not yet been elucidated, although evidence suggests a role as a lipid translocase in the retinal regenerative pathway. Our primary objective is to provide direct evidence for this putative role.
Delineating The Interaction Between The Amyloid Precursor Protein Family And SorLA-LR11
Funder
National Health and Medical Research Council
Funding Amount
$749,022.00
Summary
The Alzheimer's disease Amyloid Precursor Protein (APP) is central to the cause of Alzheimer's disease (AD). It's metabolised into the neurotoxic amyloid beta (Abeta) peptide that is deposited in AD brains. The sorLA protein is a neuronal protein that interacts with APP and alters its metabolism into Abeta. This grant will study the interaction between APP and sorLA and define the APP binding site for sorLA which represents a potential drug target.
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.
The Molecular Basis Of G Protein Coupled Transport
Funder
National Health and Medical Research Council
Funding Amount
$495,938.00
Summary
G proteins are molecular switches in all organisms, turning fundamental processes on and off . Defects in the functions of these switches can lead to severe diseases, such as cancer. Crucial details regarding the mechanism by which these switches are turned to on are still missing. This proposal will use a bacterial model system, with aims to provide structural and functional detail on the molecular mechanism of the switch in G proteins, and to extend this model to mammalian systems.