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THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providi ....THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providing only a modest survival advantage (4-6 months) has annual sales of several billion dollars. microRNA represent a relatively newly discovered form of gene activity regulation. Taking a key leadership role in this area will put Australian science at the forefront of international research initiatives.Read moreRead less
Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less
Preventing genetic damage with BIX - a novel player in the DNA damage response pathway. Defects in the DNA damage-response pathway underpin many human genetic disorders and diseases, including cancer. A detailed understanding of this process has enormous implications for future medicine. Our characterization of a novel protein involved in DNA damage signalling will help in screening inhibitors of this pathway that could be applied in chemo-and/or radiotherapy. This proposal will place Australia ....Preventing genetic damage with BIX - a novel player in the DNA damage response pathway. Defects in the DNA damage-response pathway underpin many human genetic disorders and diseases, including cancer. A detailed understanding of this process has enormous implications for future medicine. Our characterization of a novel protein involved in DNA damage signalling will help in screening inhibitors of this pathway that could be applied in chemo-and/or radiotherapy. This proposal will place Australia among the leaders in this internationally significant and highly competitive area of research leading to the creation of new compounds. Capture of this technology will create the opportunity for IP income, novel exports and new enterprises for Australia.Read moreRead less
Molecular, genetic and cellular analysis of melanisation in human pigmentation. This investigation examines variations in the genes that determine human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of ....Molecular, genetic and cellular analysis of melanisation in human pigmentation. This investigation examines variations in the genes that determine human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of ultraviolet (UV) radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less
Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases includ ....Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases including infectious disease, auto-immune disease and leukaemia, and thus a long-term outcome may be improved treatments for such disease. Read moreRead less
Progenitor cells within the peritoneal cavity. Implantation of a foreign object into the peritoneal cavity of animals recruits undifferentiated cells of bone marrow origin that encapsulate the free-floating object, then differentiate into myofibroblasts. When large pieces of myofibroblast capsule tissue are subsequently grafted into autologous artery, bladder or vas deferens, they develop the structure and morphology of that organ. We hypothesise that multipotent progenitor cells sequestered t ....Progenitor cells within the peritoneal cavity. Implantation of a foreign object into the peritoneal cavity of animals recruits undifferentiated cells of bone marrow origin that encapsulate the free-floating object, then differentiate into myofibroblasts. When large pieces of myofibroblast capsule tissue are subsequently grafted into autologous artery, bladder or vas deferens, they develop the structure and morphology of that organ. We hypothesise that multipotent progenitor cells sequestered to the peritoneal cavity can be manipulated to differentiate along smooth muscle and other pathways. The proposed project aims to identify the origin of these cells and characterise the transcriptional program that regulates their differentiation.Read moreRead less
Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that t .... Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that the true nature of brain adaptation across the lifespan will be revealed. Findings which may then provide new opportunities to strengthen, maintain and optimise cognitive function.Read moreRead less
Understanding the role of the corepressor protein KAP1 in DNA damage response pathway. Defects in the DNA damage response pathway underpin many human genetic disorders and diseases, including cancer. A detailed understanding of this process has enormous implications for future medicine. Our characterization of a new player involved in DNA damage signalling will help in screening of inhibitors of this pathway that could be applied in chemo-and/or radiotherapy. The proposal will place Australia am ....Understanding the role of the corepressor protein KAP1 in DNA damage response pathway. Defects in the DNA damage response pathway underpin many human genetic disorders and diseases, including cancer. A detailed understanding of this process has enormous implications for future medicine. Our characterization of a new player involved in DNA damage signalling will help in screening of inhibitors of this pathway that could be applied in chemo-and/or radiotherapy. The proposal will place Australia among the leaders in this internationally significant and highly competitive area of research leading to the creation of new compounds. Capture of this technology will create the opportunity for IP income, novel exports and new enterprises for Australia.Read moreRead less
The characterization of tiny Ribonucleic acids in animal epigenetics. Epigenetics, the inheritance of traits not encoded in deoxyribonucleic acid (DNA), is not well understood in animals. This project will investigate two classes of Ribonucleic acid (RNA) that may form part of an animal-specific epigenetic regulatory system. This study could revolutionize our understanding of animal genetics.
The other half of the G-protein story: Functional analysis of the plant G-protein gamma subunits. It is now established that G-proteins are involved in the transduction of a number of important processes in plants (Cell division, stomata control, defence, light perception, etc). Nevertheless the data accumulated to date is based on the study of one of the two subunits (alpha) of the G-proteins. Almost nothing is known about the role of the second (and independent) subunit: beta-gamma. We will st ....The other half of the G-protein story: Functional analysis of the plant G-protein gamma subunits. It is now established that G-proteins are involved in the transduction of a number of important processes in plants (Cell division, stomata control, defence, light perception, etc). Nevertheless the data accumulated to date is based on the study of one of the two subunits (alpha) of the G-proteins. Almost nothing is known about the role of the second (and independent) subunit: beta-gamma. We will study for the first time the role of the beta-gamma subunit in plants. We will use a comprehensive approach combining biochemical, physiological, phenotypic, genomic and proteomic studies.Read moreRead less