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Alzheimer’s disease (AD), is the most common form of dementia, accounting for between 50-70% of all cases. There is general agreement that current treatments for AD/dementia are inadequate so new treatment strategies are desperately needed. I am addressing these challenges by developing new technologies to generate next generation treatments for AD.
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
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.
Mechanism Of Action And Targeting Of RAGE In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$386,423.00
Summary
Humans have evolved defense and repair mechanisms to counteract threats such as tissue injury and infection. The immune system first must detect the potential life-threatening event and it does so by recognizing danger signals. RAGE is a key cell-surface receptor that recognises these danger signals. Despite its important role in health and disease our understanding of how RAGE works is very limited. We will discover how RAGE works and how to manipulate its function for new infection therapies.
Mechanisms Of Ligand-Selective Signalling By Chemokine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$749,428.00
Summary
Receptors are molecules located on the surfaces of cells. They control the response of one cell to chemical signals emitted by different cells. In this project we aim to characterise and understand the molecular details of how a receptor can respond differently to distinct chemical signals. The results of this study will help to guide future development of medicines to control white blood cell migration into tissues during inflammatory diseases such as heart disease, diabetes and arthritis.
Small Molecule Activators Of Glucagon-like Peptide Receptor
Funder
National Health and Medical Research Council
Funding Amount
$658,152.00
Summary
This project seeks new knowledge about (i) a protein on pancreatic cells that can be stimulated to treat problems associated with type 2 diabetes, and (ii) how to create small molecules that can act on this protein and afford a better treatment for diabetes. Advantages of such a new treatment will be low cost, easy administration as an oral tablet rather than injection, need for minimal supervision and monitoring by medical professionals, and therefore more accessibility to global populations.
Deciphering Signalling Pathways Regulating Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$407,402.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia.
Exploring The Role Of Arrcd4 In Extracellular Vesicle Biogenesis And Its Implications In Tissue Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$678,742.00
Summary
Most cells in the body release small packages known as extracellular vesicles (or EVs in short), which carry proteins and other cellular material. EVs transport important cellular messages required for the everyday function of cells and play crucial roles both in normal wellbeing and disease. This proposal will investigate how EVs are formed, how they select their protein content and how they contribute to the maturation of some cell types in the body.