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
Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. Th ....Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. The pioneering work carried out on Acropora in this laboratory suggests that it is perhaps the best choice currently available for this purpose. This project will use Acropora to address fundamental questions about the evolution of nervous system developmental processes.Read moreRead less
Function and redundancy of SOX genes in the mammalian sex determination pathway. We are studying a mouse model of abnormal sex organ development in which genetically female mice develop as males. Our basic research program will lead to greater understanding of the genetic switch controlling the formation of male and female characteristics. This research should in turn provide insight into the causes of defects in patients with disorders of sex development, helping to inform the difficult clinica ....Function and redundancy of SOX genes in the mammalian sex determination pathway. We are studying a mouse model of abnormal sex organ development in which genetically female mice develop as males. Our basic research program will lead to greater understanding of the genetic switch controlling the formation of male and female characteristics. This research should in turn provide insight into the causes of defects in patients with disorders of sex development, helping to inform the difficult clinical decisions that need to be made for their treatment, and ultimately leading to better management and therapeutic strategies. Our studies may also provide unique methods to control the exotic mouse population, using the daughterless strategy.Read moreRead less
Regulation And Role Of Transcription At The Centromere.
Funder
National Health and Medical Research Council
Funding Amount
$737,801.00
Summary
Every human cell has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome. It controls the process of cell division, and it ensures the equal division of the duplicated chromosomes. Defects in centromere function can result in various genetic diseases and development of cancers. The structure of the centromere is unique and its properties are determined by an array of proteins and other as yet unknown factors that ....Every human cell has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome. It controls the process of cell division, and it ensures the equal division of the duplicated chromosomes. Defects in centromere function can result in various genetic diseases and development of cancers. The structure of the centromere is unique and its properties are determined by an array of proteins and other as yet unknown factors that bind to it. In our preliminary work, we have demonstrated that a novel non-protein component in the form of RNA (which are expressed products of genes) is essential for the binding of key proteins to the centromere. The presence and importance of such an RNA component has not been previously suspected and represents an exciting new mechanism that help to determine the functional and structural integrity of the centromere. In this project, we propose to study the details of this RNA and to define how this RNA-related mechanism operates to ensure the proper assembly and function of the centromere during cell division.Read moreRead less
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less
Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775570
Funder
Australian Research Council
Funding Amount
$570,000.00
Summary
Purchase of a high resolution organic mass spectrometer. The diverse research supported by the new instrument is expected to encompass a wide range of beneficial outcomes in the areas of health, plant genetics and breeding, horticulture, chemistry and novel analytical technologies. Genetic studies will lead to improved plant crops and are expected to contribute to new treatments for multiple scleroris and diabetes. Investigations in organic and organometallic chemistry will lead to the productio ....Purchase of a high resolution organic mass spectrometer. The diverse research supported by the new instrument is expected to encompass a wide range of beneficial outcomes in the areas of health, plant genetics and breeding, horticulture, chemistry and novel analytical technologies. Genetic studies will lead to improved plant crops and are expected to contribute to new treatments for multiple scleroris and diabetes. Investigations in organic and organometallic chemistry will lead to the production of better materials, more efficient catalysts and novel drugs. This instrument will provide infrastructure essential to enabling researchers to maintain internationally competitive profiles in these areas.Read moreRead less
Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control h ....Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control holistic physiological responses is largely unknown. By deciphering how neural networks are formed this project aims to provide broad biological insight to wiring of the entire nervous system which is likely to have significant implications for the formation of synthetic neural networks and for regeneration.Read moreRead less