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
Is restoration working? An ecological genetic assessment. This project aims to assess the success of restoration in terms of ecological and genetic viability for plant species in the Fitzgerald River–Stirling Range region of Western Australia, where significant investment is being made in restoring connectivity at a landscape scale. The project intends to compare reproductive output, pollinator behaviour, mating, genetic diversity and pollen dispersal in restored sites with those of undisturbed ....Is restoration working? An ecological genetic assessment. This project aims to assess the success of restoration in terms of ecological and genetic viability for plant species in the Fitzgerald River–Stirling Range region of Western Australia, where significant investment is being made in restoring connectivity at a landscape scale. The project intends to compare reproductive output, pollinator behaviour, mating, genetic diversity and pollen dispersal in restored sites with those of undisturbed natural vegetation. The project moves measures of restoration success beyond that of population establishment and survival to incorporate the evolutionary processes that provide long-term resilience, persistence and functional integration of restored populations into broader landscapes.Read moreRead less
The molecular evolution of wings in flightless birds. The flightless Australian emu and New Zealand kiwi have small wings, while the extinct moa had none at all. This project will identify the genetic changes that have lead to wing reduction and loss in flightless birds. The results will shed light on the genetic control of forelimb development and how it has evolved.
The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which ....The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which sex genes are targets? Epigenetic enzymes are astonishingly conserved, providing exciting opportunities to draw from human systems to unravel novel signatures of temperature-induced sex switching in reptiles. This project will advance knowledge of developmental programming generally.Read moreRead less
Understanding the evolution of the alternation of generations in the land plant life cycle. This project will investigate the genetic basis and evolution of the land plant life cycle, in which both haploid and diploid phases consist of complex multicellular bodies. The project's findings, which will be made using two model laboratory plants, will be applicable to all plants and will help understand important processes such as pollen and seed production.
Elucidating the genetic basis of newly evolved metabolic functions in yeast. Elucidating the genetic basis of newly evolved metabolic functions in yeast. This project intends to research how complex metabolic pathways originate and evolve. This project will use cutting edge genome sequencing and molecular techniques to elucidate the heritable genetic basis of Baker’s yeast, which has been the selectively evolved to use xylose as a sole carbon source: something vital for second generation biofuel ....Elucidating the genetic basis of newly evolved metabolic functions in yeast. Elucidating the genetic basis of newly evolved metabolic functions in yeast. This project intends to research how complex metabolic pathways originate and evolve. This project will use cutting edge genome sequencing and molecular techniques to elucidate the heritable genetic basis of Baker’s yeast, which has been the selectively evolved to use xylose as a sole carbon source: something vital for second generation biofuel production that wild yeast cannot do. This project will combine detailed molecular characterisation of highly adapted yeast strains with a novel "molecular palaeontology" approach to trace the evolutionary process and identify functionally significant loci under selection. Detailed characterisation of this trait will accelerate the development of future yeast strains and test fundamental evolutionary theories.Read moreRead less
Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature ....Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature muscle types and patterns. The intended outcome of this research is to generate understanding of the complex molecular basis of muscle patterning in the simple paradigm of the zebrafish myotome that could be applied across the vertebrate phylogeny.Read moreRead less
Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the s ....Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the simpler liverworts to more complex flowering plants. The project may generate new understanding of the principles of how genes and hormones control the architecture of plant shoot systems, and support the targeted selection of new agricultural plants.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less