Effects Of The Atrial Natriuretic Factor Enhancer And The 5'HS4 Insulator On The Probability Of Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$534,628.00
Summary
Complex organisms contain many different types of cells, which can have completely different appearances and functions. All of these cells contain the same genes; the differences between them are achieved by the selective use of the genes. The means by which the selective use of genes is accomplished is a key to understanding how complex organisms develop, and how that development goes awry in cancer, heart disease, and other common disorders. A very large body of evidence indicates that gene re ....Complex organisms contain many different types of cells, which can have completely different appearances and functions. All of these cells contain the same genes; the differences between them are achieved by the selective use of the genes. The means by which the selective use of genes is accomplished is a key to understanding how complex organisms develop, and how that development goes awry in cancer, heart disease, and other common disorders. A very large body of evidence indicates that gene regulation is accomplished by the interaction of protein factors with segments of DNA flanking the gene. One hypothesis underlying our work is that the flanking DNA elements act primarily to increase the probability that a gene will be active rather than silent. We will ask if removing a known regulatory element from the gene for Atrial Natriuretic Factor (ANF) in mice reduces the likelihood of ANF being expressed by heart cells when the heart is stressed. This experiment will also shed new light on an extremely common disease state in humans (cardiac hypertrophy). In a second experiment, we will use a new experimental system we have developed to ask if a gene regulatory element is able to dial up the amount of expression from a gene, as well as to switch the gene on. Our previous work suggested this was not the case, but we wish to conduct a more rigorous test. Another hypothesis is that no DNA element is able to completely shield a transferred gene from the regulatory elements surrounding it. Accordingly, we will test a DNA element that has been proposed to insulate any gene from all influences of surrounding genes, and ask if it is able to create an autonomously expressing gene at any site within the genome. Because they deal with functions that are common to all genes, these experiments will provide information that should be applicable to a broad array of efforts to manipulate gene expression.Read moreRead less
Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous ....Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous environmental and biomedical research is built. Social impact will be seen in the training of a new generation of integrative genome biologists, and the shaping of attitudes toward the role of genetics in human biology.Read moreRead less
Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium E ....Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium Escherichia coli to elucidate the molecular strategies used in these controls. Because this protein controls the expression of a number of genes with diverse functions, evolution has selected equally diverse mechanisms to achieve appropriate transcriptional responses. The detailed knowledge of the E.coli genome and of the various genes regulated by TyrR make it an excellent system for such fundamental studies.Read moreRead less
Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the ....Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the controlled release of therapeutic compounds. The involvement of Honours and Ph.D students in this project will expose the next generation of Australian scientists to this emerging discipline. International collaboration leading to publications in high impact scientific journals will enhance Australia's scientific reputation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668440
Funder
Australian Research Council
Funding Amount
$850,000.00
Summary
Advanced technology for transcriptomics, genomics and gene mapping. Acquistion of the equipment requested in this application will maintain the expertise developed by researchers within New South Wales and attract and retain exceptional individuals who can contribute to our understanding of how genes interact with one another. The benefit of such an enhances facility will be the delivery of a better functional understanding of health and disease which will provide both community and national be ....Advanced technology for transcriptomics, genomics and gene mapping. Acquistion of the equipment requested in this application will maintain the expertise developed by researchers within New South Wales and attract and retain exceptional individuals who can contribute to our understanding of how genes interact with one another. The benefit of such an enhances facility will be the delivery of a better functional understanding of health and disease which will provide both community and national benefits. The primary purpose of this LIEF application is to standardize approaches to the study of genome function across the nodes of the Ramaciotti facility and to expand the capacities of the facility to cope with the increased demand in this technology. Read moreRead less
Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these p ....Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these populations. The goal is to understand what types of mutations are targeted by selection at the gene expression level and why.Read moreRead less
Special Research Initiatives - Grant ID: SR0354500
Funder
Australian Research Council
Funding Amount
$10,000.00
Summary
ARC Research Network in Microarray Technology. The primary aim of this proposal is to transform the premier genomic technology into a standard research tool; microarrays are now a priority for anyone studying the genetics underlying key biological processes. A principal challenge for the Australian research community is to capture all aspects of microarray technology and make them readily available. We will address these needs by developing a network to:
-establish regular research meetings,
- ....ARC Research Network in Microarray Technology. The primary aim of this proposal is to transform the premier genomic technology into a standard research tool; microarrays are now a priority for anyone studying the genetics underlying key biological processes. A principal challenge for the Australian research community is to capture all aspects of microarray technology and make them readily available. We will address these needs by developing a network to:
-establish regular research meetings,
-facilitate training in array methodologies and bioinformatics,
-co-ordinate innovation of technologies,-provide centralised data warehousing,
-provide access to automated high-level gene annotation,
-provide data mining tools,
-set standards for data management and exchangeRead moreRead less
Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.Read moreRead less