Schizophrenia affects, on average, 1% of the population over a lifetime and accounts for 2.6% of the global burden of disease and disability, according to a joint study by the World Health Organization and the World Bank. It is a complex disorder involving both genetic and environmental risk factors, but the specific causation remains poorly understood. People with schizophrenia experience symptoms such as delusions and hallucinations, distorted perception of reality, and progressive loss of mot ....Schizophrenia affects, on average, 1% of the population over a lifetime and accounts for 2.6% of the global burden of disease and disability, according to a joint study by the World Health Organization and the World Bank. It is a complex disorder involving both genetic and environmental risk factors, but the specific causation remains poorly understood. People with schizophrenia experience symptoms such as delusions and hallucinations, distorted perception of reality, and progressive loss of motivation, which disrupt personal development. Recent research demonstrates that underlying cognitive impairments, affecting reasoning, memory, planning ability and information processing, are at the core of the disorder and account for a high proportion of these handicaps. In a study involving 112 families with members suffering from schizophrenia, Western Australian researchers carried out detailed investigations of brain cognitive functioning, coupled with a complete genome scan. They identified, in about 50% of these families, a variety of schizophrenia characterized by multiple cognitive deficits, which turned out to be linked to a particular segment of chromosome 6. It was exactly in the chromosomal region where US investigators had previously found genetic linkage with the symptoms of schizophrenia in a large series of Irish families. In this project, the Western Australian and US teams, together with a group of Dutch researchers, will embark on a joint search for the gene (or genes) on chromosome 6, contributing to cognitive deficits in schizophrenia. They will assess a further large series of patients and controls, and conduct molecular genetic studies aiming to pinpoint the specific gene defect or variant. If successful, the project will have far-reaching implications for defining novel drug targets and treatment strategies for this disabling disorder.Read moreRead less
Discovery And Analysis Of Vertebrate Intestinal Development Genes That May Play A Role In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$376,613.00
Summary
Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities ( ....Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities (mutations) that are acquired over the course of a lifetime. Together the mutated genes produce changes in cell behaviour in processes such as growth, migration, angiogenesis (the ability to attract a blood supply) and cell death. All of these processes are active during normal development of a vertebrate organism, but are generally shutdown in the adult state, except in cancer. In this study we will analyse a group of genes that we have recently shown to be indispensable for normal intestinal development in zebrafish. Zebrafish are small tropical fish that are used frequently for genetic studies. They are very closely related to mammals and it has been shown that the genetic pathways that control the development of this animal are highly conserved in fish and mammals. Importantly, the genetic pathways that lead to cancer in humans are also strikingly similar in zebrafish. Our experiments will use mouse models to discover whether the zebrafish genes we have identified can lead to cancer when they are aberrantly expressed in the intestines of mice. Any genes that are found to contribute to the development of cancer in these models could become potential new targets for cancer therapy.Read moreRead less
The Cellular And Molecular Basis To The Paradox Of Positive Versus Negative T Cell Selection
Funder
National Health and Medical Research Council
Funding Amount
$278,090.00
Summary
The protection against disease requires the generation of white blood cells called T lymphocytes that are produced in the thymus. Each T cell has a specific surface receptor, generated by random gene switching, that can react against foreign pathogens. Since there is a very high conservation of molecules used in all organisms, some of these receptors could by chance also react against normal cells in the host. Eliminating all such self-reactive cells would mean, however, the repertoire remaining ....The protection against disease requires the generation of white blood cells called T lymphocytes that are produced in the thymus. Each T cell has a specific surface receptor, generated by random gene switching, that can react against foreign pathogens. Since there is a very high conservation of molecules used in all organisms, some of these receptors could by chance also react against normal cells in the host. Eliminating all such self-reactive cells would mean, however, the repertoire remaining for eliminating infection would be too low and immunodeficiency develops. This project investigates the mechanisms controlling the balance between defence infection and the need to prevent immune-based self destruction termed autoimmunity.Read moreRead less
What Triggers Complex Regional Pain Syndrome After Minor Injury?
Funder
National Health and Medical Research Council
Funding Amount
$958,898.00
Summary
Most people recover from minor trauma but some develop very disabling, difficult to treat, costly pain syndromes. We can identify those at high risk of developing such a syndrome after wrist fracture. By comparing inflammation, immune system function, stress, brain function and behaviour between high and low risk patients, we will take a major step towards understanding, preventing and treating these syndromes.