Glaucoma is the second leading cause of blindness in the world affecting approximately 70 million people. Glaucoma can occur at any age but the commonest type occurs in middle to old age. The disease has a genetic basis and can be inherited. As a result we have been studying the genetics of the disease in two large families from Tasmania. We hope to identify the genes involved in disease causation using a number of genetic techniques. Once mutations in a disease gene have been identified from af ....Glaucoma is the second leading cause of blindness in the world affecting approximately 70 million people. Glaucoma can occur at any age but the commonest type occurs in middle to old age. The disease has a genetic basis and can be inherited. As a result we have been studying the genetics of the disease in two large families from Tasmania. We hope to identify the genes involved in disease causation using a number of genetic techniques. Once mutations in a disease gene have been identified from affected individuals we will then be in a position to look for mutations in other family members and identify those individuals at risk of developing disease. Improvements in our understanding of how these genes are involved in disease causation will allow us to offer diagnostic testing to the wider community and develop better therapeutic interventions for treatment.Read moreRead less
Identification Of A Genetic Defect Characterized By Radiosensitivity And Defective P53 Stabilization
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identifica ....Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identification of new syndromes with radiosensitivity assists in delineating the overall response to radiation and the connection with cancer. This project is designed to identify the molecular basis of what appears to be a novel defect. It has some of the characteristics of a well described syndrome ataxia-telangiectasia (A-T), namely signs of neurodegeneration and sensitivity to radiation but the protein defective in A-T appears to have normal function in this case. A comprehensive investigation of a number of pathways of radiation signaling is planned to identify the nature of the defect.Read moreRead less
Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood for ....Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood formation will be studied. We will establish techniques for several steps that will be useful for all zebrafish mapping projects. We expect the genetic characterization of these mutants to provide new insights into nerve cell survival, gut development, and blood formation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775587
Funder
Australian Research Council
Funding Amount
$532,000.00
Summary
Correlating Genomics and Proteomics for Systems Biology: integrating the '-omics'. Acquisition of the infrastructure requested will maintain and extend the expertise developed by researchers in NSW and will allow retention and attraction of leading researchers who can contribute to understanding how genes and proteins interact in the development of the organism - the central focus of systems biology. The enhancement of the facility will allow a better understanding of biomolecular interactions ....Correlating Genomics and Proteomics for Systems Biology: integrating the '-omics'. Acquisition of the infrastructure requested will maintain and extend the expertise developed by researchers in NSW and will allow retention and attraction of leading researchers who can contribute to understanding how genes and proteins interact in the development of the organism - the central focus of systems biology. The enhancement of the facility will allow a better understanding of biomolecular interactions in health and disease, providing both community and national benefits. The focus of this LIEF application is to provide infrastructure platforms for the study of the systems biology of organisms and additional capacity by the facility for the expected increased demand for this technology in this new area. Read moreRead less
Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the form ....Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the formulation of new research hypotheses, enriching the curriculum and the provision of informed counselling. The embryological expertise developed for this project will enhance the nation's research capability through the sharing of skills and knowledge with a national network of academic and industrial research teams. Read moreRead less
A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate ou ....A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate outcome is a better understanding of the regulation of our immune system. This approach will fuel the discovery of new signalling molecules & their effects on a population of cells, & likewise provides a novel approach to study the dysregulation of cell signalling pathways.Read moreRead less
Fine Scale Mapping And Identification Of The IBD1 Gene On Chromsosome 16
Funder
National Health and Medical Research Council
Funding Amount
$483,849.00
Summary
One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more th ....One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more than 10,000 Australians who suffer from IBD. The existence of a genetic predisposition to IBD is now well established, and there is strong evidence that the disease is complex, resulting from the interaction of a number of different genes. To date, one genetic localisation on chromosome 16 has been established in several different populations, and we have confirmed the importance of this localisation in the Australian population. We will further refine the localisation by fine scale mapping in the pericentromeric region of chromosome 16 by identifying and studying the inheritance of novel markers in the region. We will then identify and characterise the gene itself using several complementary appoaches that rely on differences at the molecular level between disease and normal tissue. This work is part of the international effort to identify all IBD susceptibility genes. Once that is achieved, approaches to explaining the interactions between the genes, their protein products and environmental triggers can be determined. Only when the mechanisms of these interactions are understood will the expectation of rational therapies based on an understanding of disease aetiology be possible.Read moreRead less
Genetic variation of transcriptional control. Genetic variation is a key cause phenotype differences in humans, animals, and plants and so of great economic importance. Despite its proven importance to human diseases, ?quantitative? variation in the amount of gene expression rather than ?qualitative? protein sequence changes, has not been systematically studied. We have developed a powerful method to identify genetic causes of quantitative variation using crosses of inbred mice in conjunction wi ....Genetic variation of transcriptional control. Genetic variation is a key cause phenotype differences in humans, animals, and plants and so of great economic importance. Despite its proven importance to human diseases, ?quantitative? variation in the amount of gene expression rather than ?qualitative? protein sequence changes, has not been systematically studied. We have developed a powerful method to identify genetic causes of quantitative variation using crosses of inbred mice in conjunction with microarray techniques to analyse expression of thousands of genes simultaneously. These studies will be extended to humans and be significant to wide areas of biological and commercial activity.Read moreRead less
Statistical Advances in the Post-Genome Era. Biologically relevant statistical foundations for post-genome biology and biotechnology will be developed. Specific goals of the topics include the development of accurate and more efficient algorithms for sequence alignments, improved models to maximise the accuracy of analyses for gene expression data and superior statistical methods for identification of complex gene networks that predispose an organism to disease. The Project will make significant ....Statistical Advances in the Post-Genome Era. Biologically relevant statistical foundations for post-genome biology and biotechnology will be developed. Specific goals of the topics include the development of accurate and more efficient algorithms for sequence alignments, improved models to maximise the accuracy of analyses for gene expression data and superior statistical methods for identification of complex gene networks that predispose an organism to disease. The Project will make significant contributions to the new and evolving priority research area of Bioinformation Science (including bioinformatics). Outcomes will include novel techniques for analysis and mining of post-genome data, with applications to developments in Bio-medicine and Bio-agricultureRead moreRead less
Histone H3.3 Dynamics At The Telomere In Pluripotent Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$571,977.00
Summary
The telomere is required for the protection of the chromosome ends. Telomere loses its repeat during each cell division, so telomere shorthening is one of the mechanisms underlying organismal aging as critically short telomeres induce chromosome instability and cell death. Defective telomeres can also result in genetic diseases and development of cancers. Here, we propose to study the mechanism that operates to ensure continual telomere renewal without senescence in embryonic stem cells.