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
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
Novel Vitamin E Analogues with Enhanced Specificity for Malignant Cells. The aim of this project is to synthesise and characterise novel compounds based on vitamin E succinate that are capable of efficiently and selectively killing cancer cells. The new compounds will be tested for their ability to induce programmed cell death in cancer cells and the most active of them will be also tested for anti-cancer effect in a pre-clinical model. We believe that novel analogues based on vitamin E succinat ....Novel Vitamin E Analogues with Enhanced Specificity for Malignant Cells. The aim of this project is to synthesise and characterise novel compounds based on vitamin E succinate that are capable of efficiently and selectively killing cancer cells. The new compounds will be tested for their ability to induce programmed cell death in cancer cells and the most active of them will be also tested for anti-cancer effect in a pre-clinical model. We believe that novel analogues based on vitamin E succinate can lead to the discovery of very effcient and selective anti-cancer drugs with no side-effects that may be used for patient treatment in the future. This makes our project of exceptional significance.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
Functional and structural characterisation of Defective embryo and meristems (Dem) proteins involved in plant development. The proposed research will lead to advances in understanding the regulation of plant development, a process impacting on agriculture, environmental management and human health, areas designated as national research priorities. This understanding is required for modifying plant growth and architecture to fit particular environments, for example generating plants with more ext ....Functional and structural characterisation of Defective embryo and meristems (Dem) proteins involved in plant development. The proposed research will lead to advances in understanding the regulation of plant development, a process impacting on agriculture, environmental management and human health, areas designated as national research priorities. This understanding is required for modifying plant growth and architecture to fit particular environments, for example generating plants with more extensive and deeper roots to mine the soil moisture and nutrients to enhance crop productivity in Australia, and maintaining the competitive advantage of Australian agriculture in view of the range of environmental conditions encountered in this country. The project will also contribute to the health of the Australian population through consumable plants in the diet.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less