New Antioxidants Impacting on ROS and Free Radical Mediated Cellular Damage and Disease. Oxidative stress describes the condition where free radicals damage cells and biological systems and this stress underlies many diseases including neurological conditions and aging disorders such as Alzheimer's Disease. This project sets out to create new forms of powerful antioxidant drugs able to probe the mechanisms of such diseases with the view to developing new treatments and therapies.
Functional characterisation of CMAP, a novel centrosome- and midbody-associated protein. Cell division is a highly regulated process involving many components to produce two daughter cells which contain an equal amount of DNA. Thus incorrect localisation and modification of specific proteins that regulate this process cause cell division errors resulting in genomic instability. We have recently identified a novel protein called CMAP that is involved in the final stages of cell division, which in ....Functional characterisation of CMAP, a novel centrosome- and midbody-associated protein. Cell division is a highly regulated process involving many components to produce two daughter cells which contain an equal amount of DNA. Thus incorrect localisation and modification of specific proteins that regulate this process cause cell division errors resulting in genomic instability. We have recently identified a novel protein called CMAP that is involved in the final stages of cell division, which involves the cleavage of the cell membrane to produce two daughter cells. Here, we aim to characterise the mechanism(s) of CMAP function and to identify and characterise CMAP binding proteins to further understand the mechanisms involved in the final stages of cell division to maintain genomic stability.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
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
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.
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Structural studies on carbohydrate modifying enzymes. Carbohydrates form one of four major classes of biological macromolecules, and are major targets for drug design. We have developed methods for the production of carbohydrate synthesising enzymes and will determine the structures of these enzymes to provide the foundation for structure based design of inhibitors. The research will allow us to understand how these enzymes function in normal circumstances and how they malfunction in disease sta ....Structural studies on carbohydrate modifying enzymes. Carbohydrates form one of four major classes of biological macromolecules, and are major targets for drug design. We have developed methods for the production of carbohydrate synthesising enzymes and will determine the structures of these enzymes to provide the foundation for structure based design of inhibitors. The research will allow us to understand how these enzymes function in normal circumstances and how they malfunction in disease states such as cancer. The long-term outcome will be a significantly enhanced body of knowledge of this poorly understood group of enzymes and the development of new carbohydrate based chemicals with novel therapeutic applications.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