The Role Of Plasma Membrane Microdomains In Cellualar Function
Funder
National Health and Medical Research Council
Funding Amount
$4,083,868.00
Summary
The planned research program relates to novel hypotheses regarding the role of cell surface domains in organising signalling pathways at the cell surface. The proposal will involve identifying the domains and molecules involved in specific signalling pathways and dissecting the formation and function of surface structures called caveolae. The findings will have huge importance for therapeutic strategies aimed at combating the cellular changes associated with cell transformation in cancer and oth ....The planned research program relates to novel hypotheses regarding the role of cell surface domains in organising signalling pathways at the cell surface. The proposal will involve identifying the domains and molecules involved in specific signalling pathways and dissecting the formation and function of surface structures called caveolae. The findings will have huge importance for therapeutic strategies aimed at combating the cellular changes associated with cell transformation in cancer and other human diseases.Read moreRead less
This established team of investigators will research into the molecular control of white blood cell formation and function, using a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes. The team will also attempt to identify new validated targets for therapeutic intervention by using both forward and reverse genetic approaches in mice coupled with complete phenotypic analyses of the blood cell system.
Control Of Cell Proliferation And Differentiation In Breast And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$5,043,011.00
Summary
Breast and prostate cancer are the most commonly diagnosed cancers in women and men respectively, together accounting for >25% of all newly diagnosed cancers in Australia and other developed countries. Although significant improvements in the management of these cancers have occurred in the past 20 years further research is needed to better understand the molecular mechanisms of disease development and progression. Such research is critical to the better management and ultimate control of the ....Breast and prostate cancer are the most commonly diagnosed cancers in women and men respectively, together accounting for >25% of all newly diagnosed cancers in Australia and other developed countries. Although significant improvements in the management of these cancers have occurred in the past 20 years further research is needed to better understand the molecular mechanisms of disease development and progression. Such research is critical to the better management and ultimate control of these diseases through better treatments and prevention. A multidisciplinary team of cancer researchers at the Garvan Institute of Medical Research, with a 10 year track record of discovery and application of their research into breast and prostate cancer, will employ state-of-the-art research tools to identify new molecules and molecular pathways involved in these diseases. This new information will facilitate the improved management of these cancers through improved assessment of disease progression at the time of diagnosis and the development of new drugs and strategies for treatment and prevention.Read moreRead less
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
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.
Understanding G Protein-Coupled Receptors (GPCRs): Accelerating Discovery From Concept To Clinic.
Funder
National Health and Medical Research Council
Funding Amount
$6,871,789.00
Summary
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors (and thus drug targets) in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Our Program addresses this knowledge gap, using GPCR models that are relevant to treatment of metabolic, cardiovascular and central nervous system 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