Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis ....Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis here will be in the relationship between the two proteins in co-ordinating the repair of breaks in DNA. This information will be important in understanding mechanisms for maintaining the integrity of the genome.Read moreRead less
The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims t ....The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims to look at the mechanisms that exist to prevent this initial loss of genetic material within an individual cell. It further aims to translate theses discoveries into the clinic, providing new tools for diagnosis and prognosis of specific cancers and to establish links with major pharmaceutical companies to develop novel anticancer therapies.Read moreRead less
Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex ....Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex intracellular signalling networks. This is an important step towards identifying new drug targets that are responsible for tumour growth. Australian science will benefit from the training of new scientists in modern, post-genome technologies where there is currently a world shortage of experienced personnel.Read moreRead less
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
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
Investigating the role of gene loops in regulating gene expression. The ability to identify functional variants in regulatory elements will have implications for researchers in multiple fields of biology, from molecular medicine to agriculture. Transfer of expertise and application of the knowledge generated by our research to such fields stands to improve diagnosis of disease predisposition and to improve quality of animal and plant products. These outcomes will benefit all Australians. This kn ....Investigating the role of gene loops in regulating gene expression. The ability to identify functional variants in regulatory elements will have implications for researchers in multiple fields of biology, from molecular medicine to agriculture. Transfer of expertise and application of the knowledge generated by our research to such fields stands to improve diagnosis of disease predisposition and to improve quality of animal and plant products. These outcomes will benefit all Australians. This knowledge will also improve the education of Australian University students as it contributes to the development of advanced curricula and access to more powerful research methods. In addition, the project will foster important collaborations between Australian researchers and those overseas.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561173
Funder
Australian Research Council
Funding Amount
$207,189.00
Summary
High throughput proteomics - Thermo Finnigan ProteomeX LCQ Integrated Proteomics Workstation. As research in the biological sciences moves into post-genomics era, so attention has focused on the development of technologies capable of characterizing the molecular complexity inherent in the proteome. Recent technical innovations in this field have resulted in the advancement of mass spectrometers that are capable of exemplifying unknown proteins with great efficiency. These new technologies are ....High throughput proteomics - Thermo Finnigan ProteomeX LCQ Integrated Proteomics Workstation. As research in the biological sciences moves into post-genomics era, so attention has focused on the development of technologies capable of characterizing the molecular complexity inherent in the proteome. Recent technical innovations in this field have resulted in the advancement of mass spectrometers that are capable of exemplifying unknown proteins with great efficiency. These new technologies are central to any institution committed to the development of a competitive research nexus in biological sciences. The purpose of this application is to upgrade the mass spectrometry facility at the University of Newcastle such that it is able to provide cutting edge support to the extensive scientific community within the Hunter region.Read moreRead less
Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in ....Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in order to develop more potent drug analogues. Development of these molecules will involve a collaborative and multidisciplinary link with our industry partner and the use of frontier technologies that may lead to improved health and economic outcomes for Australia. Read moreRead less
Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry ....Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry for targeted drug design, which could realise benefits in the form of novel medical treatments and reduced side effects. The monolayer template technology will also extend the capabilities of the National Cryo-EM facility, the infrastructure of which, is open for all Australian researchers. Read moreRead less
Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less