Regulation Of Gene Expression: Biomolecular Interactions In Cellular Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,998,713.00
Summary
This team consists of three of Australia�s younger researchers Merlin Crossley, Joel Mackay and Jacqui Matthews (as Chief Investigators), who are recognized as authorities in the areas of gene regulation and the structural and functional analysis of proteins. They are joined by Mitchell Weiss, a world authority on blood development and clinical disorders,and Alexis Verger, a molecular and cell biologist recruited from France, both as Principal Investigators. Crossley, Mackay and Matthews have wo ....This team consists of three of Australia�s younger researchers Merlin Crossley, Joel Mackay and Jacqui Matthews (as Chief Investigators), who are recognized as authorities in the areas of gene regulation and the structural and functional analysis of proteins. They are joined by Mitchell Weiss, a world authority on blood development and clinical disorders,and Alexis Verger, a molecular and cell biologist recruited from France, both as Principal Investigators. Crossley, Mackay and Matthews have worked as a team for around six years to date, have published together in high-quality international journals, and have received anumber of accolades for their contributions to Australian science. For example, Crossley has won a number of national awards, including the Gottschalk Medal of the Australian Academy of Science; Mackay was recently awarded the Prime Minister�s Prize for Life Scientist of the Year, and Matthews won the only Charles and Sylvia Viertel Medical Research Fellowship to be awarded in 2003. The members of this team have collaborated extensively on the world stage and Crossley, Mackay and Matthews have also taken leadership roles in the Australian scientific community. Mitchell Weiss has been an important collaborator, exchanging reagents and advice, since he and Crossley trained together as postdocs in Stu Orkin�s lab at Harvard in the early 90s. Most recently Weiss, in collaboration with Mackay, has made important discoveries on a-globin production, which has led to several highly significant publications including a seminal paper in Cell in 2004.The program of research put forward in this proposal centres around understanding the mechanisms through which genes are switched on and off, using blood development as a model system, that is also fundamental to human life. The regulation of gene output is essential both during the development of an organism and throughout the course of its life. Problems with this regulation can result in many different disease states, most notably cancer, which includes the many different types of leukemias. At one level, gene output is controlled by networks of specific proteins known as transcription factors that interact both with each other and with DNA. Currently, however, the details surrounding which complexes regulate which genes and the processes that control the making and breaking up of the complexes are not well understood. Knowledge of how these interactions take place will put us in a position to control the output of chosen genes for therapeutic purposes. We propose to use a combination of cell biological, biochemical, and structural approaches to firstly shed light on these complexes and secondly develop reagents that can be used to manipulate the activity of specific genes.Read moreRead less
Proteases, Their Inhibitors And Receptors In Degenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,843,388.00
Summary
Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin super ....Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin superfamily of protease inhibitors and their protease partners. He is currently the scientific director of the Victorian Bioinformatics Consortium and an NHMRC Senior Research Fellow. Dr Bird is an NHMRC Senior Research Fellow who discovered the intracellular branch of the serpin superfamily and formulated the hypothesis that describes their function. A-Prof Mackie is a world expert in the field of musculoskeletal biology and pathology. Dr Bottomley is a Senior Logan Fellow and RD Wright Fellow whose research focuses upon how proteins misfold and lead to disease. Dr Pike is an enzymologist whose research area encompasses a wide range of bacterial and mammalian proteases involved in the pathology of human disease. Each individual in this team brings different skills which makes this a very important and powerful collaboration. The research is extensive and involves protein folding, enzyme kinetics, molecular modelling, structural biology, bioinformatics, cell biology and pathology, enzyme kinetics and drug design. Collectively the CI’s have a total of 154 papers since 1998, of which a third include two or more of the CI’s as co-authors. Currently the team holds over >$5 million in grant funding. The team is augmented by four P.I.s: Dr Buckle is a talented structural biologist; Dr Scott is a molecular cell biologist who holds an NHMRC CJ Martin Fellow; Dr Garcia de la Banda is a computer scientist based at Monash and Dr Grigoryev is a world expert in chromatin condensation based at Penn State University (USA).Read moreRead less
This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� c ....This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� cells that can rapidly become antibodyproducing cells should the same infection occur again in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an antibody-producing cell, by studying the genes that are known to be required for the cells to form, or to do their work. We will study animals whose immune systems are under- or over-active, to find out what part of the antibody-producing process is faulty. Using this information, we hope eventually to be able to study diseases of antibody producing cells in humans (as occur in allergy, asthma, rheumatoid arthritis and leukaemia), to be able to identify the precise cause of the problem, and to suggest a therapy. This information may also be used to improve the outcome of vaccination where an enhanced antibody response is desired.Read moreRead less
Sexually Transmitted Infections: Causes, Consequences And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$9,784,331.00
Summary
Sexually transmitted infections are important causes of serious illness and death in Australia and overseas with high or rising rates of treatable or preventable diseases in a number of populations, Particularly affected in Australia are young people, Aboriginal and Torres Strait Islander communities, and homosexual men. We will bring together a new team of researchers to discover new information about how to prevent and manage these infections.
Individual Decision Making, Welfare Measurement And Policy Evaluation In The Health Sector: A Microeconometric Approach
Funder
National Health and Medical Research Council
Funding Amount
$6,968,101.00
Summary
This proposed program of research will contribute to the development of economics and health economics internationally. It provides an exciting opportunity to bring together scholars across economics at the forefront of the discipline internationally, who are researchers with extensive experience in the practical application of research results in shaping policy directions. The approach will fill the repeatedly identified gap in policy relevant health services research at the system level in Aus ....This proposed program of research will contribute to the development of economics and health economics internationally. It provides an exciting opportunity to bring together scholars across economics at the forefront of the discipline internationally, who are researchers with extensive experience in the practical application of research results in shaping policy directions. The approach will fill the repeatedly identified gap in policy relevant health services research at the system level in Australia. The immediate outcomes of the research program will be information on specific health policy issues, in terms of the drivers of cost and utilization, access and equity.Read moreRead less
Atherosclerosis:Lipoproteins, Cell Biology And Vascular Physiology
Funder
National Health and Medical Research Council
Funding Amount
$7,274,391.00
Summary
The team comprises internationally recognised experts in basic, clinical and public health applied research in cardiovascular disease, particularly atherosclerosis that is the commonest cause of death in Australia and other developed countries. Over the last decade, improvement in cardiovascular health has been primarily the result of a better understanding on how to control 'bad' (or LDL) cholesterol. The significance of the proposed studies is that, on the one hand, they will provide new infor ....The team comprises internationally recognised experts in basic, clinical and public health applied research in cardiovascular disease, particularly atherosclerosis that is the commonest cause of death in Australia and other developed countries. Over the last decade, improvement in cardiovascular health has been primarily the result of a better understanding on how to control 'bad' (or LDL) cholesterol. The significance of the proposed studies is that, on the one hand, they will provide new information on how 'good' lipoproteins protect us from atherosclerosis. This information can then be used to regulate 'good' cholesterol in a meaningful manner. On the other hand, the proposed studies will provide fundamental insights into how a range of lifestyle factors, physiological processes and pathological conditions relate to both the function of blood vessel-lining cells and susceptibility of individuals to atherosclerosis.Read moreRead less
Molecular Mechanisms Of Cardiac Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,213,642.00
Summary
Heart disease remains the leading cause of death in our society. Almost two million Australians suffer from the debilitating effects of heart disease and it is the leading cause of premature permanent disability in our workers. Heart defects are also the most common type of birth defect and the leading cause of deaths in infants dying from birth defects. Many of these problems can be attributed directly to defects in the development, repair and-or function of heart muscle and, at the cellular le ....Heart disease remains the leading cause of death in our society. Almost two million Australians suffer from the debilitating effects of heart disease and it is the leading cause of premature permanent disability in our workers. Heart defects are also the most common type of birth defect and the leading cause of deaths in infants dying from birth defects. Many of these problems can be attributed directly to defects in the development, repair and-or function of heart muscle and, at the cellular level, of heart muscle cells or cardiomyocytes. Understanding the cardiomyocyte as well as integrated heart development, biology, physiology and function, therefore, holds great promise for major advances in the prevention and treatment of contemporary heart diseases. This Program Grant brings together a unique team of interactive researchers with expertise in cardiovascular physiology, as well as developmental, cellular and molecular biology. The outcomes anticipated from new insights into heart biology that will result from the proposed studies, are the development of novel therapeutic approaches for the prevention and treatment of heart attacks and heart failure.Read moreRead less