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
Cleavage Methods Of Mutation Detection: Improvement And Application In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,044,349.00
Summary
Genes contain the information to build our body and keep it operating normally. These genes are inherited from our parents and number around 100,000. Faults in these genes can cause inherited diseases such as cystic fibrosis, cancers and common disorders such as Asthma and diabetes. These genes need detecting so that particular genes can be identified as causing the disease and also so that patients can have their disease properly diagnosed so that proper therapy and information can be given to ....Genes contain the information to build our body and keep it operating normally. These genes are inherited from our parents and number around 100,000. Faults in these genes can cause inherited diseases such as cystic fibrosis, cancers and common disorders such as Asthma and diabetes. These genes need detecting so that particular genes can be identified as causing the disease and also so that patients can have their disease properly diagnosed so that proper therapy and information can be given to the patients. In future similar changes (but changes not causing disease) may be searched for in patients to overcome the side effects of drugs. Our centre specializes in the methods of detecting faults and their application. Two of our methods are being used around the world and one is being sold as simple kit. These methods still have drawbacks and the work proposed is to overcome some of these. We propose to apply our and other methods to faults in genes which have recently been shown to cause diseases of the artery. This is an exciting new development that shows that this disease is similar to cancer. We are fortunate to have attracted Dr Paula Bray from the laboratory which discovered this. This new finding needs to be studied in more detail and may identify life-style factors which cause coronary heart disease. Our studies will also assist in gene therapy when it becomes available.Read moreRead less
Genome-wide Association Studies Of Biomedical Traits And Endophenotypes For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,804.00
Summary
The burden of common complex diseases, such as cardiovascular disease is substantial to the health care system. These diseases are caused by genes and environments as well as their interactions. The proposed project will identify genes affecting the susceptibility of individuals to complex diseases. Discovery of such genes will be important for their diagnosis, prevention and treatment and may serve as an important resource for future personalized medicine.
Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide ....Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide a short-cut to the cloning of one such gene. We have started with the mouse version, which is lost in leukemic cells. We have mapped the gene to within a very small chromosomal region, and we have identified a biological effect which correlates with loss of the gene. Our next step is to combine these two approaches to clone the gene. Because these genes are always highly conserved between species, we will be able to quickly clone the corresponding human gene, the loss of which is very likely to be important in cancer of various types.Read moreRead less
The properties of Vegf-B suggest that it may play a role in new blood vessel formation (angiogenesis) especially during the development of the heart. Mice with the Vegf-b gene deleted are viable and fertile but display cardiac dysfunction as the animals age and in experimental conditions of ischemia. Comparison of total gene expression in the hearts of mice lacking Vegf-B with those of normal mice will identify genes involved in blood vessel formation during cardiac development and maintenance. ....The properties of Vegf-B suggest that it may play a role in new blood vessel formation (angiogenesis) especially during the development of the heart. Mice with the Vegf-b gene deleted are viable and fertile but display cardiac dysfunction as the animals age and in experimental conditions of ischemia. Comparison of total gene expression in the hearts of mice lacking Vegf-B with those of normal mice will identify genes involved in blood vessel formation during cardiac development and maintenance. The genes identified will be targets for designing potential new drugs and therapies for cardiovascular disease.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
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
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
I am a clinician-scientist and endocrinologist most interested in clinical problems associated with bone, in particular the highly heritable disease of osteoporosis. I hope by studying genetic determinants of bone mass to determine the key genes involved, with the long term aim of informing the development of novel therapies for this common, painful and disabling disease.
Genetic And Bioinformatic Analysis Of Complex Human Diseases
Funder
National Health and Medical Research Council
Funding Amount
$8,752,567.00
Summary
Some human diseases are common in families; examples include prostate cancer, blood cancers, epilepsy and diabetes. Therefore, close relatives of individuals with a disease have an increased risk of being affected by this disease, implying a genetic basis. Finding the cause of these diseases is difficult, we will be developing novel approaches to the identification of genes responsible for these diseases. This is the first step towards the development of treatments for affected individuals.