Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the ....Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the identification of the genetic basis of the disease has proved exceedingly difficult, with numerous studies producing no definitive data. The lack of convincing results has been interpreted as an indication of complex genetic mechanisms and underlying differences between affected families and ethnic groups. Genetically isolated populations, where most individuals descend from a small number of founders, are believed to hold great potential for understanding the genetic basis of complex diseases, such as bipolar disorder. Affected subjects in such populations are likely to share the same predisposing genes, making these genes easier to identify. During the last 10 years, we have been involved in the study of bipolar disorder in one such population, with very promising results. In this project, we propose to take the research further by collecting more affected families, confirming the current positive findings and narrowing down the search to a small region, possibly a single gene. If successful, the study will be a major breakthrough which, by identifying a molecular pathway and disease mechanism, will contribute valuable and generally valid information on the biological basis of mood disorders.Read moreRead less
Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease le ....Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease leading to the potential identification of new drug and vaccine targets. The methodologies and expertise developed will be used will be available to other research groups working on infectious diseases.Read moreRead less
Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's ne ....Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's near neighbours, this project will strengthen Australia's international leadership in this field. Our study will provide, for the first time for any helminth parasite, a freely available genetic database that profiles the gene expression repertoire of individual parasite tissues, a development likely to enhance the international effort in controlling these harmful diseases.Read moreRead less
MitoGenomics of Key Pathogens - An International Research Co-operative. The national/community benefits are: (1) to develop a long-term, high quality scientific and technological program contributing to national objectives, including the maintenance of a strong capability in basic research, the development of new scientific concepts and the enhancement of international collaborative links; (2) to strengthen the links between basic and applied research; (3) to develop excellence in research by pr ....MitoGenomics of Key Pathogens - An International Research Co-operative. The national/community benefits are: (1) to develop a long-term, high quality scientific and technological program contributing to national objectives, including the maintenance of a strong capability in basic research, the development of new scientific concepts and the enhancement of international collaborative links; (2) to strengthen the links between basic and applied research; (3) to develop excellence in research by promoting collaborative research, resulting in a more efficient use of resources in a national and international context; (4) to enhance the skills-base in biology and biotechnology; (5) to substantially increase global visibility through quality research, leading to an increased investment in Australian science.Read moreRead less
Insect age: an ecological genomics approach to understanding host-parasite interactions. The importance of insect age (or the age structure of a population of insects) in understanding relationships between insects and their abiotic and biotic environment has been stressed in many theoretical studies but seldom directly tested. This is because few tools exist that can accurately measure the age of a wild-caught insect with any accuracy. In this proposal we plan to use a genomics approach to deve ....Insect age: an ecological genomics approach to understanding host-parasite interactions. The importance of insect age (or the age structure of a population of insects) in understanding relationships between insects and their abiotic and biotic environment has been stressed in many theoretical studies but seldom directly tested. This is because few tools exist that can accurately measure the age of a wild-caught insect with any accuracy. In this proposal we plan to use a genomics approach to develop tools that can be used to efficiently determine the age of an insect and then apply these tools to better understand the relationship between insect age and the ability of an insect to transmit pathogens to humans, livestock or plants. These tools will also have future applicability in developing new approaches to control insect transmitted disease as well as provide methodology to determine the effectiveness of current control programs that seek to kill pest insect populations of agricultural or public health significance.Read moreRead less
Identifying Novel Genes Causing Cytochrome C Oxidase (COX) Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$426,917.00
Summary
Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the uniqu ....Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the unique mitochondrial DNA we inherit only from our mothers. Many more genes await discovery. This study focuses on the mitochondrial disorder cytochrome c oxidase (COX) deficiency, for which we have diagnosed 80 Australian patients. COX requires 13 separate components to be assembled together in order to work properly, but mutations in the genes encoding these components are not present in most patients. We believe that the most common problems will be in genes involved in assembling the components rather than in the components themselves. We will use a number of methods to pinpoint where in the genome the disease genes are located. A key to our strategy is identifying patients likely to have mutations in the same gene. We have identified two such groups, and will do studies that involving fusing two cell lines together to confirm they have the same disorder. We will then perform genetic mapping to look for regions of similarity in the genome using DNA (SNP) chips. We will test how well the genes in such regions are expressed, whether we can correct the problem in cultured skin cells by introducing a healthy copy of that chromosome, and look for gene mutations. Identifying these genes will allow us to improve future diagnosis and prevention and may allow us to develop new methods of treatment. Milder mitochondrial problems also contribute to a range of more common diseases such as diabetes and Alzheimer disease, so any new treatments could potentially have wide applicationRead moreRead less
Genetic and epigenetic control of developmental competence. Development is an important biological process of life and understanding development has important medical and economic benefits for Australia. This research aims to study development using a simple, easily manipulated and well established experimental organism, a fungus, as a model for development in other organisms, including humans. In addition, fungi directly impact on life at many levels. Fungi can be pathogens of humans, other ani ....Genetic and epigenetic control of developmental competence. Development is an important biological process of life and understanding development has important medical and economic benefits for Australia. This research aims to study development using a simple, easily manipulated and well established experimental organism, a fungus, as a model for development in other organisms, including humans. In addition, fungi directly impact on life at many levels. Fungi can be pathogens of humans, other animals or plants significantly affecting our health, agriculture and industry. Fungi are also beneficial to other organisms, especially to many plants, and are used to manufacture pharmaceuticals and enzymes used in the health and biotechnology industries.Read moreRead less
Australian plague locust population genetics and migratory behaviour. The project will allow improved monitoring and forecasting of locusts in Australia and thereby help prevent locust outbreaks. Benefits will arise directly through greater effectiveness in reducing locust damage to crops, and indirectly to Australian rural industry generally through the economic benefits of reduced losses and locust control costs. Environmental and social benefits will also arise from reduced, better targeted u ....Australian plague locust population genetics and migratory behaviour. The project will allow improved monitoring and forecasting of locusts in Australia and thereby help prevent locust outbreaks. Benefits will arise directly through greater effectiveness in reducing locust damage to crops, and indirectly to Australian rural industry generally through the economic benefits of reduced losses and locust control costs. Environmental and social benefits will also arise from reduced, better targeted use of chemical insecticides. This in turn can produce secondary economic benefits, e.g. through enhanced growth and profitability of the organic beef industry within the main locust-outbreak area. Read moreRead less
Rapid mapping of genes for complex traits. This project will develop a new resource that will allow rapid identification of genes controlling complex traits. This world-leading resource will improve knowledge of diseases like diabetes and neurological diseases.