Structure and function of a new class of multi-zinc finger (MZF) transcriptional regulators. An understanding of how genes are switched on and off during the development and lifetime of an organism is central to developing the ability to fight many diseases in a rational way. This project will advance our knowledge in this area at a fundamental molecular level by examining the mechanisms through which a specific set of proteins controls gene expression.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.
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
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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New Strategies for Monitoring DNA-Anticancer Drug Interactions. The highly successful cisplatin works by binding to DNA and partially unwinding or bending the DNA. As a consequence of the success if cisplatin, alternative anticancer drugs are being developed with reduced side effects for patients. One of the bottom necks in the development of alternative drugs is rapid screening of the efficacy on new leads. The proposed research will develop new technologies for monitoring DNA-drug binding, ....New Strategies for Monitoring DNA-Anticancer Drug Interactions. The highly successful cisplatin works by binding to DNA and partially unwinding or bending the DNA. As a consequence of the success if cisplatin, alternative anticancer drugs are being developed with reduced side effects for patients. One of the bottom necks in the development of alternative drugs is rapid screening of the efficacy on new leads. The proposed research will develop new technologies for monitoring DNA-drug binding, DNA damage and DNA repair using novel DNA biosensors. the novelty of the biosensor technology will be to use the modulation of charge transfer through DNA as a method for determining the structural changes that occur in DNA due to these events occurring.Read moreRead less
High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to b ....High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to be used anti-cancer agents. This project represents an opportunity for Australia to take a significant, innovative lead in the development of hitherto unforseen therapeutic agents.Read moreRead less
Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding ....Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding protein domains with the goal of selectively blocking these inappropriate interactions. Additionally, these engineered proteins have potential uses as biochemical tools such as to help delineate the functions of natural proteins with no known functions.Read moreRead less
Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the ....Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the passage of cells through the cell cycle so that repair can occur. This project studies the mechanism of action of one of these enzymes which will be of benefit in designing new compounds to fight disease. Read moreRead less
An Automated Bioimaging System for High-Content Cell-Cycle Screening. 1) Providing a better understanding of the biological complexities
that will advance knowledge in life science research and facilitate the development of new anti-cancer drugs.
2) Supporting Australian academic institutions in a challenging field of innovative research through international, interdisciplinary collaborations, and publications in journals of high quality scientific research.
3) Providing research training ....An Automated Bioimaging System for High-Content Cell-Cycle Screening. 1) Providing a better understanding of the biological complexities
that will advance knowledge in life science research and facilitate the development of new anti-cancer drugs.
2) Supporting Australian academic institutions in a challenging field of innovative research through international, interdisciplinary collaborations, and publications in journals of high quality scientific research.
3) Providing research training in a research venture that requires expertise and collaboration in the disciplines of biology, engineering, computer science, and mathematics.
4) Bringing economic and social benefits for Australia by enhancing important industries and existing technologies in medicine, and biotechnology.
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Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins ....Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins of interest by conventional proteomic methods. The establishment of SELDI-MS as a viable tool for cell proteomics would open new opportunities to understand a broad range of cellular functions at the level of protein expression.Read moreRead less