Multiscale Analysis Of Plasma Membrane Microdomains In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
The cell surface encloses the cell in a protective barrier but it must also respond to signals coming from outside the cell. To accomplish this, the cell surface is made up of numerous regions each with a specialised role. This proposal aims to examine how lipids and proteins work together to make these specialised regions and aims to understand what goes wrong in diseases such as muscular dystrophy.
The regulation to early T cell signalling is a critical step in immune responses. Superimposed onto the biochemical pathways is a spatial organization that defines the immunological synapse. My research aims to map the principles of the spatial organization on the molecular scale to identify how lipids could unbalance the dynamic signalling equilibrium, for example in obese patients. To achieve this goal, my research group has developed single molecule microscopy approaches.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.
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.
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.
A Novel Mechanism For Regulating Membrane Proteins By Ubiquitin Ligases And Their Adaptors
Funder
National Health and Medical Research Council
Funding Amount
$627,897.00
Summary
Many membrane proteins act as ion channels, transporters or receptors for extracellular ligands and are critical to normal functioning of the cell. These proteins are generally regulated by transport to or from the membrane to ensure that correct levels are maintained at the membrane. This proposal is to study a novel way of regulating membrane proteins. The successful completion of the work will provide important knowledge relevant to many human diseases.
The Role Of The Glutamine Transporter SNAT3 In Ion Transport, Cell Signaling And Ammonia Detoxification
Funder
National Health and Medical Research Council
Funding Amount
$393,249.00
Summary
Hepatic encephalopathy is a syndrome observed in patients with liver cirrhosis and is caused by increased amounts of ammonia in the blood. The proposed project investigates a transporter that is involved in ammonia and glutamine metabolism in liver and brain. The two organs are critical to the pathology of liver failure and ammonia toxicity resulting from reduced liver function. The transporter thus could become a drug target for a variety of liver diseases.
Atherosclerosis is the disease which narrows arteries and causes heart attacks and stroke. It is one of the major causes of death in Australia. Although certain treatments, such as lowering blood cholesterol levels, reduce the incidence of atherosclerosis, current motality rates from this disease indicate that there is still a great need to improve our understanding and treament of the condition. In the development of atherosclerosis, some of the cells in the vessel wall accumulate large deposit ....Atherosclerosis is the disease which narrows arteries and causes heart attacks and stroke. It is one of the major causes of death in Australia. Although certain treatments, such as lowering blood cholesterol levels, reduce the incidence of atherosclerosis, current motality rates from this disease indicate that there is still a great need to improve our understanding and treament of the condition. In the development of atherosclerosis, some of the cells in the vessel wall accumulate large deposits of cholesterol. These cells are macrophages, derived from circulating white blood cells that have migrated into the vessel wall. Normally these cells are able to efficiently export excess cholesterol, but this process seems to fail in atherosclerosis. This project will study the molecular mechanism for cholesterol export from macrophages, concentrating on a the mechnisms by which recently identified cholesterol pumps operate. These are located in cell membranes, including at the cell surface, which is the site at which cholesterol is transferred to acceptors such as HDL and apoAI. By understanding how these pumps work, and how their activities are controlled, we will be better able to devise ways to increase their efficiency in atherosclerosis, and so to prevent the tissue cholesterol accumulation that drives this disease.Read moreRead less