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Interrogation Of Two Novel Genetic Susceptibility Loci For Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$840,615.00
Summary
This proposal, from the Australia and New Zealand multiple sclerosis (MS) Genetics Consortium, aims to interrogate two new genes that it recently identified as predisposing for the development of MS. Both of the genes underlying these findings are also associated with risk of developing other autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and Graves' disease.
Climate Change And Rural Communities: Integrated Study Of Physical And Social Impacts, Health Risks And Adaptive Options
Funder
National Health and Medical Research Council
Funding Amount
$611,599.00
Summary
Rural Australia has begun to experience climate change impacts - which will increase in future. Losses in farm yields, water supplies, property, community morale and family incomes have diverse health effects. We will study the separate and joint effects of climate change and associated extreme events (e.g., bushfires) on selected health outcomes. Using integrative methods, we will clarify the main influences on health risks, their future projections, and how best to intervene to lessen risks.
Myosin VI: A Novel Molecular Apparatus For Epithelial Cohesion
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Adhesion between cells holds the human body together and affects many aspects of our health including normal tissue and organ function. Conversely, loss of normal cell-cell adhesion contributes to major diseases, including cancer and inflammation. One key molecule, E-cadherin, is necessary for many epithelial organs and its function is perturbed in disease. This research project addresses how E-cadherin works with a cellular motor, Myosin VI, to maintain the integrity of epithelial tissues.
Adhesion between cells is important during health and disease. Cell-cell interactions are necessary both as the embryo forms and to preserve tissues and organs in later life. Important disease states arise when cell-cell adhesion is broken. Only by understanding the molecular mechanisms that hold cells together can we analyse how they are perturbed to cause diseases such as cancer and inflammation.
Regulation Of Dynamic Cell-cell Adhesions By Coordinated Action Of Lipid Kinases And Phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$529,565.00
Summary
This research project studies the molecular mechanisms that allow cells to attach to, and recognize, one another. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside on the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, to adhere to each other. By this means, populations of individual cells can be linked together into cohesive populations - i.e. the tissues and organs of the body. The importance of cadherin adhesion i ....This research project studies the molecular mechanisms that allow cells to attach to, and recognize, one another. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside on the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, to adhere to each other. By this means, populations of individual cells can be linked together into cohesive populations - i.e. the tissues and organs of the body. The importance of cadherin adhesion is exemplified by the fact that disruption of cadherin adhesion contributes to many important diseases, especially inflammation and cancer. Thus understanding how cadherins hold cells together is necessary for us to understand the molecular basis of common diseases. In this project we study how cadherins signal to regulate cellular behaviour. We build on our recent discovery that E-cadherin can activate a lipid in the cell membrane, PIP3, that is known to be a key regulator of many cellular activities. We aim to understand how this signal is generated in response to E-cadherin adhesion and how it elicits normal cellular responses to cadherin adhesion.Read moreRead less
Preserving Barriers: How Cadherin Signaling Coordinates Dynamic Adhesion And Tight Junction Assembly In Epithelial Cell.
Funder
National Health and Medical Research Council
Funding Amount
$557,939.00
Summary
Epithelia protect the body from its environment. Breakdown of the epithelial barrier in tissues such as the skin and intestine, as occurs in burns and inflammation, leads to invasion of bacteria and severe metabolic disturbances. In this project we study the cell signaling mechanisms that maintain epithelial barriers in healthy tissues that undergo turnover and remodelling. Understanding these signaling pathways provides a foundation to understand how they are perturbed in disease.
Cortactin: Integrating Cadherin Signalling For Junctional Integrity
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Adhesion between cells holds the human body together and affects many aspects of our health, including normal tissue and organ function. Importantly, loss of normal cell-cell adhesion contributes to many diseases, including cancer and inflammation. One key adhesion molecule, E-cadherin, is necessary for many epithelial tissues and its function is perturbed in disease. This research project addresses how E-cadherin signals into cells to control cell-to-cell interactions.
Cloning Of Human NK Cells And Macrophages Carbohydrate Receptors
Funder
National Health and Medical Research Council
Funding Amount
$489,750.00
Summary
Lymphocytes, also known as white blood cells, are important for the well being of all individuals as these are the cells which fight infection by microorganisms. The lymphocyte gets its information about enviroment and communicates with other cells using molecules on the cell surface. We are examining a group of molecules found on the surface of different lymphocytes which bind different sugars, and also to characterised new cell surface molecules that interact with carbohydrates. These studies ....Lymphocytes, also known as white blood cells, are important for the well being of all individuals as these are the cells which fight infection by microorganisms. The lymphocyte gets its information about enviroment and communicates with other cells using molecules on the cell surface. We are examining a group of molecules found on the surface of different lymphocytes which bind different sugars, and also to characterised new cell surface molecules that interact with carbohydrates. These studies will examine the structure of the the molecules that interact with with sugars, in order to understand how these give messages to the lymphocyte to trigger various functions that these cell perform in the immune response. We will isolate the genes for these and study their function in greater detail. The cell surface carbohydrate receptors represents several different families of molecules, it is highly likely that these have important roles in the immune response. The potential significance of studying these lymphocyte cell surface molecules is in defining the functional properties of these molecules, the results of which will give us novel insights into the molecular mechanisms involved in the generation of immune responses, the mechanism of immuno deficiency and autoimmunity.Read moreRead less
Function And Regulation Of ATM: Mechanistic Studies
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
The human genetic disorder ataxia-telangiectasia is characterised by neurodegeneration, immunodeficiency, radiosensitivity and a very high risk for development of cancer. The gene product defective in this syndrome, ATM, was identified in 1995 and since then its role in protecting the cell against genetic damage has been investigated in some detail. The ATM protein is a very large molecule and to date only one functional region has been described. It is very likely that other regions of the mole ....The human genetic disorder ataxia-telangiectasia is characterised by neurodegeneration, immunodeficiency, radiosensitivity and a very high risk for development of cancer. The gene product defective in this syndrome, ATM, was identified in 1995 and since then its role in protecting the cell against genetic damage has been investigated in some detail. The ATM protein is a very large molecule and to date only one functional region has been described. It is very likely that other regions of the molecule will be important in its function in the cell. This project is designed to investigate the importance of other domains in the protein and also what it is that causes ATM to be activated. We have developed a methodology which allows us to introduce changes anywhere in the ATM gene and then test the effects of these changes in a biological read-cut assay. This approach will enable us to ascribe functional significance to any region of ATM. We will focus on regions where we have some preliminary evidence for activity. Finally we will carry out a mechanistic study to see how ATM is activated. These data will be useful in future design of molecules to interfere with the function of ATM in applications designed to make tumours more receptive to radiotherapy.Read moreRead less
A Single Nucleotide Resolution Map Of A Cancer Associated Neochromosome
Funder
National Health and Medical Research Council
Funding Amount
$567,350.00
Summary
Neochromosomes (NCs) are large chromosomes which are not usually found in a normal cell. Well differentiated liposarcoma (WDLPS) is a tumour which is almost universally associated with the presence of NCs. We are using the approach of purifying the NC from a series of WDLPS cell lines, and using new techniques to derive the DNA sequence of the neochromosome. We will use this information to identify the genetic factors on the NC which are involved in the initiation or progression of WDLPS.