Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events inv ....Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events involved in controlling gene expression during development and differentiation. Results from this project will also provide new insights into the 'multifunctionality' of cellular proteins and will illustrate the importance of RNA studies in molecular medicine.Read moreRead less
This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does ....This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does not achieve this through changing genetics the library always stays intact. Rather, it acts by using proteins or chemicals to make DNA functional in one way, or another. Genomic imprinting is a special type of epigenetics. While an embryo has received identical genetic information from each of its parents, the epigenetic information received from each parent was not entirely the same. Some genes which behave differently according to what parent they came from. For example, a gene that makes a growth factor protein is active only if received from the father. If received from the mother, it is inactive, and makes no protein. Genes behaving in this way are known as imprinted genes. We are trying to discover what epigenetic mechanisms are behind this behaviour of imprinted genes. One way we are approaching this problem is to study germ cells the cells giving rise to eggs and sperm. These cells are unusual in that their imprinted genes behave in the same way regardless of whether they were received from the mother or father, i.e., like any other gene. If we can understand why this is the case, we will be better able to understand why imprinted genes behave the way they do in the rest of the cells of the body. Broadly, the mechanisms we uncover should further our understanding of germ cell development, gene expression, and disease. Perturbations in the epigenetic profile are likely causes of human disease, including cancer.Read moreRead less
Determining the regulation of vitamin D metabolism. The proposed project will lead to a better understanding of factors that influence the biological function of vitamin D. This will impact in several areas of human health and will provide new avenues for the development of preventative approaches and treatment of cancer. This project is based on the use of 'Frontier Technologies' that will be applied to elucidate basic biological questions.
PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity ....PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity by identifying physiologic agonists of the PKC-zeta-phospho-Sp1 axis and FasL-dependent apoptosis, interactions of phospho-Sp1 with the authentic FasL promoter and its recruitment of collaborative factors. The commercial exploitation of phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys will generate economic returns to Australia.Read moreRead less
PKC-zeta-dependent Sp1 phosphorylation: Identification of phosphorylated amino acids, demonstration of functional significance, generation and use of novel phospho-specific Sp1 antibodies. Sp1 is a widely expressed transcription factor that controls the basal expression of virtually every mammalian gene, including that of PDGF-B. We recently reported that PDGF-B expression atypical protein kinase C-zeta phosphorylation of Sp1. Building on these seminal findings, this project will first, delinea ....PKC-zeta-dependent Sp1 phosphorylation: Identification of phosphorylated amino acids, demonstration of functional significance, generation and use of novel phospho-specific Sp1 antibodies. Sp1 is a widely expressed transcription factor that controls the basal expression of virtually every mammalian gene, including that of PDGF-B. We recently reported that PDGF-B expression atypical protein kinase C-zeta phosphorylation of Sp1. Building on these seminal findings, this project will first, delineate the specific amino acid residues in the zinc finger region of Sp1 phosphorylated by PKC-zeta; second, demonstrate the functional importance of these site-specific modifications in the PKC-zeta-Sp1-PDGF-B system and the expression of other genes, and third, generate and use novel antibodies uniquely recognising phosphorylated Sp1 as molecular and diagnostic agents.Read moreRead less
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.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
Regulation of Stress Hormone Receptors in the Brain. Our research will provide information on how the brain controls our response to stress and will allow the development of targeted strategies to reduce the possibility during chronic stress of the development of conditions such as anxiety and depression. This will improve mental health outcomes in Australia and add to Australia's economic and social stability.
The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less