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
CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research wil ....CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research will provide new data on the fundamental cellular and molecular events that are required to trigger the birth, differentiation and conditions for growth of new neurons in the adult nervous system. The generation of such insights will be critical for any translational research.
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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
Novel vitamin E analogues disrupt autocrine signalling and angiogenesis: Mechanistic studies and relevance to cancer management. Breast and mesothelioma cancers present a severe problem in Australia and many patients succumb due to lack of appropriate treatment. We believe that vitamin E analogues, selective drugs efficient against cancer cells, hold a promise as future drugs against these two pathologies. Vitamin E analogues act by several mechanisms, including toxic effect on the cancer cells ....Novel vitamin E analogues disrupt autocrine signalling and angiogenesis: Mechanistic studies and relevance to cancer management. Breast and mesothelioma cancers present a severe problem in Australia and many patients succumb due to lack of appropriate treatment. We believe that vitamin E analogues, selective drugs efficient against cancer cells, hold a promise as future drugs against these two pathologies. Vitamin E analogues act by several mechanisms, including toxic effect on the cancer cells and also on cells that are necessary for efficient progression of tumours, such as cells of the malignant blood vessels. Results of this project will be used to prepare clinical testing of these highly promising drugs.Read moreRead less
Developing efficient cancer therapies by targeting of vitamin E analogues to mitochondria. We propose a new strategy of developing efficient anti-cancer agents. Results of this project will lead to establishing highly proising anti-cancer drugs and will open new approaches for the design of novel agents that efficiently kill cancer cells.
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
Enhancing Erythropoietin Therapy In Ischaemia-reperfusion Injury Of Heart And Kidney
Funder
National Health and Medical Research Council
Funding Amount
$361,021.00
Summary
Heart attacks and kidney disease from a lack of blood flow are common causes of morbidity and have poor treatment options. Erythropoietin (epo) is a useful new treatment, but there remain some caveats to its use in humans: eg. it may cause excessive scarring during repair. Use of epo with an anti-inflammatory drug may decrease scarring and provide benefit to long-term health. We plan to carefully define the biomolecular pathways of injury and repair, to better plan this therapy for human use.
The function of truncated MEK1 protein in a G2 phase cell cycle delay and in mitosis. Understanding cell proliferation. Intracellular signaling pathways controlling cell growth are often mutated in cancers and other hyperproliferative diseases. Understanding precisely how these pathways operate and how mutations of these pathways can contribute to uncontrolled growth can readily provide new targets for preventative therapies or cures. We have identified a novel mechanism regulating one compone ....The function of truncated MEK1 protein in a G2 phase cell cycle delay and in mitosis. Understanding cell proliferation. Intracellular signaling pathways controlling cell growth are often mutated in cancers and other hyperproliferative diseases. Understanding precisely how these pathways operate and how mutations of these pathways can contribute to uncontrolled growth can readily provide new targets for preventative therapies or cures. We have identified a novel mechanism regulating one component of a well studied pathway, the MAPK pathway, and new functions for this component. The contribution of this novel component to mechanisms involved in regulating cell growth previously through to be controlled by the canonical MAPK pathway could change our understanding of the fundamental mechanisms controlling cell growth. Read moreRead less
Function of the unique mitotic form of MEK. Many of the mechanisms controlling normal cell growth and division are known, although there are an increasing number of examples of mechanism having more thn the originally defined functions. We have found that one well studied mechanism, the Ras-Raf-MEK-ERK pathway operates in a unique manner during the phase when cell division occurs, known as mitosis. Understanding this novel mechanism and identifying its function at this critical stage of cell d ....Function of the unique mitotic form of MEK. Many of the mechanisms controlling normal cell growth and division are known, although there are an increasing number of examples of mechanism having more thn the originally defined functions. We have found that one well studied mechanism, the Ras-Raf-MEK-ERK pathway operates in a unique manner during the phase when cell division occurs, known as mitosis. Understanding this novel mechanism and identifying its function at this critical stage of cell division will provide insights into how cell control the partitioning of replicated genome and produce two identical daugther cells.Read moreRead less
The role of heparan sulfate proteoglycans in the control of osteoblast phenotype. Very little is known about how bone cells progress from a naive precursor state, through differentiation and then maturation into adult cells. We wish to purify sugars from the bone cell membrane, extracellular matrix and culture medium, and examine the cellular response following the addition of these various sugar fractions to osteoblast cell cultures in combination with known growth factors. If we can control ....The role of heparan sulfate proteoglycans in the control of osteoblast phenotype. Very little is known about how bone cells progress from a naive precursor state, through differentiation and then maturation into adult cells. We wish to purify sugars from the bone cell membrane, extracellular matrix and culture medium, and examine the cellular response following the addition of these various sugar fractions to osteoblast cell cultures in combination with known growth factors. If we can control the progression of osteoblastic cells through the phases of recruitment, proliferation, differentiation and maturation by the addition of specific sugar fractions then we can potentially control bone formation.Read moreRead less