Regulator Of G-protein Signalling-5: A Key Modulator Of Vascular Maturation And The
Funder
National Health and Medical Research Council
Funding Amount
$548,396.00
Summary
Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein ....Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein which appears to be very important for normalisation, a process which is currently not well understood. This proposal continues our pioneering work on vessel normalisation and will use models of highest clinical relevance to study the dynamics of vessel remodelling in tumours. Our approach is different to current angiogenesis research which simply tries to block or destroy the blood vessels that feed tumours. We expect our findings to lead to highly specific and effective anti-tumour therapies. Moreover, vessel growth in tumours has striking parallels to other vascular processes in the body, which have important implications for major and common human diseases such as high blood pressure and atherosclerosis. We now have the tools to study these processes and their abnormalities in our newly established disease model. By gaining insight into these disorders we will be able to develop novel approaches to stop disease progression.Read moreRead less
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
Regulation of DNA replication initiation during Drosophila development. This proposal addresses the fundamental issue of the regulation of DNA
replication during development, using the animal model system, Drosophila melanogaster. This research uses a whole animal genetic and cell biological approach to explore DNA replication regulatory mechanisms that are present in multicellular organisms but not in yeast. The work undertaken here will make a significant contribution to our understanding of ....Regulation of DNA replication initiation during Drosophila development. This proposal addresses the fundamental issue of the regulation of DNA
replication during development, using the animal model system, Drosophila melanogaster. This research uses a whole animal genetic and cell biological approach to explore DNA replication regulatory mechanisms that are present in multicellular organisms but not in yeast. The work undertaken here will make a significant contribution to our understanding of DNA replication regulation within a developing organism that will be relevant to all animals.Read moreRead less
Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctora ....Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctoral researchers in the disciplines of Molecular Genetics, Molecular & Cellular Biology, Developmental Cell Biology, Mass Spectrometry and Proteomics, which will be of immense benefit to their scientific careers and the Australian scientific community.Read moreRead less
Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulat ....Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulations over the first 5 days of mouse pregnancy on embryonic temporal and spatial organisation.Read moreRead less