Probing membrane rafts using surface-selective multi-dimensional microscopy. The results of this project will provide fundamental insights into the role played by domains in cell membranes in the regulation of membrane protein function. These insights will create new avenues in the biotechnology industry for development of novel therapeutics aimed at disruption of membrane protein-protein interactions that cause aberant cell signalling in disease states such as cancer.
Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The ....Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The current study will investigate the structural and biophysical properties of a recently discovered HuR/PCBP/mRNA complex implicated in the regulation of androgen receptor expression. This information has the potential to assist in the development of drugs to reduce AR expression in prostate cancer.Read moreRead less
The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these ....The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these subcellular organelles affect free radical damage and aging, using the fruitfly Drosophila melanogaster as a model organism.Read moreRead less
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by ....Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by FOXO proteins. Although very basic in nature, these projects will identify how FOXO proteins regulate muscle cell building and wasting and, therefore, present a potential therapeutic target for muscle wasting diseases, making this project highly significant.Read moreRead less
Mechanisms of cell death regulation by the Bcl-2 protein family. Through the proposed study, the expected outcome is a better understanding of the important process of how the Bcl-2 family of proteins interact with each to control cell death. Furthermore, as dysfunctional apoptosis signalling contributes to diseases such as autoimmune conditions, neurodegenerative disorders and cancer, a detailed and sound understanding of how the cell death machinery operates should enable the design of more ef ....Mechanisms of cell death regulation by the Bcl-2 protein family. Through the proposed study, the expected outcome is a better understanding of the important process of how the Bcl-2 family of proteins interact with each to control cell death. Furthermore, as dysfunctional apoptosis signalling contributes to diseases such as autoimmune conditions, neurodegenerative disorders and cancer, a detailed and sound understanding of how the cell death machinery operates should enable the design of more effective and importantly, safer therapies against these pathologies.Read moreRead less
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theo ....Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theory. This should help to rationalise and direct funding supplied to these areas. The second benefit is for Australia: aging is a fruitful area for research because of the high general public interest and for training because of its multidisciplinary nature, and funding in Australia is very low by international standards. Read moreRead less
Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will th ....Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will then be able to be tested for their ability to act as specific drug delivery systems for use in the treatment of solid tumours.Read moreRead less
Characterisation of Bioadhesives from Marine diatoms. Biofouling occurs at great expense to governments and industry, adding up to 60% annually to the cost of propulsive fuel consumption in shipping. Diatoms include the most common algal biofoulers of natural and artificial surfaces (e.g. ship hulls). The structure of diatom adhesives will be elucidated in order to determine the molecular basis of their adhesive properties. As diatoms are capable of reversible adhesion, an understanding of th ....Characterisation of Bioadhesives from Marine diatoms. Biofouling occurs at great expense to governments and industry, adding up to 60% annually to the cost of propulsive fuel consumption in shipping. Diatoms include the most common algal biofoulers of natural and artificial surfaces (e.g. ship hulls). The structure of diatom adhesives will be elucidated in order to determine the molecular basis of their adhesive properties. As diatoms are capable of reversible adhesion, an understanding of this mechanism may enable development of strategies to counter adhesion in antifouling products (e.g. paints). This knowledge will contribute to development of new adhesives or strategies to modify and/or prevent adhesion.Read moreRead less