Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a fra ....Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a framework to test regulatory network models and to analyse the molecular basis of interactions between control systems. This research will eventually provide the ability to predict how cells respond to drugs and other environmental stimuli.Read moreRead less
How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by wh ....How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by which clusterin effects its protective actions. We expect to demonstrate that clusterin protects cells form stresses by exerting its chaperone action at or near the cell surface and to identify specific regions and structural features of the clusterine molecule important in its chaperone action.Read moreRead less
How sexually antagonistic genes and sexual selection influence the evolution of the Y chromosome. Sexually antagonistic genes are beneficial to members of one sex, but costly to the other. They are of significance both to the coevolution between the sexes and the evolution of the sex chromosomes. We will measure the sexually antagonistic effects of genes that make male guppies sexually attractive. We will then study how these genes, and the process of sexual selection that favours them influence ....How sexually antagonistic genes and sexual selection influence the evolution of the Y chromosome. Sexually antagonistic genes are beneficial to members of one sex, but costly to the other. They are of significance both to the coevolution between the sexes and the evolution of the sex chromosomes. We will measure the sexually antagonistic effects of genes that make male guppies sexually attractive. We will then study how these genes, and the process of sexual selection that favours them influence the process of recombination between the X and Y chromosomes.Read moreRead less
Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 ....Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 proteins from diverse species. We will characterise the consequences of mutations in this domain in mouse models and search for interacting proteins. Results will advance our understanding of gene regulation in the context of heart disease.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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Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation tec ....Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation techniques. The project, based on two related equine herpesviruses, will identify new targets for antiviral drugs or vaccines. These herpesvirus BAC systems represent frontier science that greatly facilitates the study of links between genome and phenome.Read moreRead less
Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second ....Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second function of these enzymes, namely their ability to break down organophosphorus-containing insecticides and nerve agents. Ultimately, the structural information resulting from this project may be used in drug design to regulate blood pressure and in engineering proteins for bioremediation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882512
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefit ....Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefits to the wider community. The application aims to enhance existing genomic technologies by adding platforms that will increase the scope of experiments that can be performed as well as providing automation and increased capacity to handle the increasing demand for these techniquesRead moreRead less
Glycine Transporters regulate the concentration of glycine in the spinal cord and brain. It has been suggested that elevating glycine levels in these regions may be useful in treating pain and schizophrenia. This project will provide the basis for the development of new glycine transport inhibitors that may be used to treat these conditions.