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
This program, run by an established team with skills in public health, clinical epidemiology, biostatistics, health economics and behavioural science addresses the under-researched issues of whether, when and how to use medical tests. The elements of the program follow the sequence in which testing is often done: for screening (early detection), for diagnosis on which to base treatment decisions, and for monitoring the effects of treatment. A common approach throughout is the identification of t ....This program, run by an established team with skills in public health, clinical epidemiology, biostatistics, health economics and behavioural science addresses the under-researched issues of whether, when and how to use medical tests. The elements of the program follow the sequence in which testing is often done: for screening (early detection), for diagnosis on which to base treatment decisions, and for monitoring the effects of treatment. A common approach throughout is the identification of the benefits and harms of testing and assessing their trade-off; how benefits weigh up against harms. This research is relevant to all partners in healthcare, (consumers, clinicians and policy-makers), who currently are being tested or using tests without being fully informed about the accuracy and effects of these tests.Read moreRead less
Advances In Clinical Trials Research And Evidence Based Decision Making
Funder
National Health and Medical Research Council
Funding Amount
$6,712,859.00
Summary
The NHMRC Clinical Trials Centre at the University of Sydney aims to use clinical trials and methodological research in trials to improve health in Australia and internationally It is a member of many international collaborative trials groups, especially in heart disease and cancer. A particular area of interest is patient preferences and decision making, particularly in cancer. The Clinical Trial Centre is active in using data from its own and other clinical trials in combined analyses to arriv ....The NHMRC Clinical Trials Centre at the University of Sydney aims to use clinical trials and methodological research in trials to improve health in Australia and internationally It is a member of many international collaborative trials groups, especially in heart disease and cancer. A particular area of interest is patient preferences and decision making, particularly in cancer. The Clinical Trial Centre is active in using data from its own and other clinical trials in combined analyses to arrive at better evidence.Read moreRead less
Health Outcomes Monitoring And Evaluation: Learning About Activity, Nutrition, Diet And Social Factors
Funder
National Health and Medical Research Council
Funding Amount
$7,486,989.00
Summary
Diabetes, Heart and Kidney disease occur in epidemic proportions among Indigenous Australians. Of particular concerns is the early age of onset of conditions that are to disease of older adulthood in the broader Australian community. While these chronic diseases are known to cause premature death and suffering in Aboriginal and Torres Strait Islander communities, there are gaps in our knowledge. For example, we know very little about how these conditionsdevelop over time in different populations ....Diabetes, Heart and Kidney disease occur in epidemic proportions among Indigenous Australians. Of particular concerns is the early age of onset of conditions that are to disease of older adulthood in the broader Australian community. While these chronic diseases are known to cause premature death and suffering in Aboriginal and Torres Strait Islander communities, there are gaps in our knowledge. For example, we know very little about how these conditionsdevelop over time in different populations. Probably the greatest knowledge gap is the area of effective intervention - both to prevent to prevent diabetes, kidney and heart disease in young people, and to treat existing cases effectivly. The main goal of this program is to bring together a multi skilled team of researchers to better understand the development of these chronic disease across the lifespan ( including differences between different populations), and to guuide the development of diet, lifestyle, and clinical interventions. Such interventions need to be simple, effective, acceptable to Indigenous people and able to be sustained over the long term. All interventions will be rigorously evaluated. The results will inform policies in ares such as quality and affordability of the food supply in remote communnities; infrastructure to promote physical activity; and provision of high quality primary health care focussing on early intervention and care of people at risk of chronic disease.Read moreRead less
Control Of Proteases In Infectious, Degenerative And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$11,668,789.00
Summary
Proteases are enzymes that control key processes in humans. The research in this program will result in major discoveries in the field of proteases and their inhibitors, with a focus on inflammatory, cardiovascular and degenerative disease. The knowledge gained from this strong foundation of fundamental research will underpin the translational outcomes necessary to combat the debilitating effects of immunological dysfunction, conformational and cardiovascular disease.
Molecular And Functional Characterisation Of Cell Surface Microdomains
Funder
National Health and Medical Research Council
Funding Amount
$4,803,731.00
Summary
This research program aims to gain a detailed understanding of the organisation of the cell surface at the molecular level. The cell surface is organised into domains with distinct functions. Visualisation of these domains, identifying their important components, and understanding how they form and function will have huge importance for therapeutic strategies aimed at combating the changes associated with cell transformation in cancer and in other human diseases such as muscular dystrophy.
Structural Biology Of Cytokine Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$3,988,996.00
Summary
This Program will be focused on a group of protein hormones and their receptors, implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine the mechanism of receptor activation and in particular will seek to link different forms of receptor assembly to different functions. This information will help us develop new drugs with more specificity for certain hormone functions and thus less side-effects.
Colon Cancer: Receptors, Signalling And Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$7,115,542.00
Summary
This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell gr ....This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell growth, survival and movement. Newly developed instruments and techniques will allow us to identify and detect the critical steps during the development of colorectal cancer and to design potent drugs to fight the disease. We have experience in conducting novel clinical trials in colon cancer and have developed imaging techniques for monitoring the effectiveness and safety of new anti-cancer drugs. Our collective scientific experience and ability to work in the clinic provides a unique opportunity for developing more effective treatments for colorectal cancer patients.Read moreRead less
The Biology & Therapeutic Manipulation Of Lymphatic Vessels In Cancer & Lymphedema
Funder
National Health and Medical Research Council
Funding Amount
$2,589,101.00
Summary
This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distan ....This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distant sites in the body, and for lymphedema, a condition in which lymphatic dysfunction leads to swelling of tissues. This program will explore the molecular mechanisms that control the growth and differentiation of the lymphatic vessels. It will greatly enhance our understanding of lymphatic vessel growth (lymphangiogenesis) and generate a range of reagents for stimulating or inhibiting this process. These reagents will be tested in animal models for their capacity to modulate lymphatic function in the context of cancer and lymphedema.Read moreRead less