Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great pot ....Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.Read moreRead less
Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet ....Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet poorly understood issue in mitochondrial genomics and evolutionary biology. Knowledge from this project will also improve our understanding of other important issues that are associated with animal mitochondria; like the mechanisms of mitochondrial disease and ageing, and the evolution of modern humans and other animals.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
Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric i ....Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric instability and the insertion of transposable elements, a dynamic balance between structural conservation and rapid evolution. This is a rare opportunity to understand the forces at work in moulding eukaryotic sub-telomeric sequences because Giardia is not constrained by sexual homogenisation and the dynamic variability is retained.Read moreRead less
Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also d ....Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also determine the functional activities of different venoms and their components. This will not only help the understanding of the medical consequences of the annual thousands of fish envenomings but also explore a largely unstudied resource for the discovery of new pharmacological diagnostics and therapeutics.Read moreRead less
Co-evolution of the host pathogen interaction between Leptosphaeria maculans and Brassica species. Brassica canola is Australia's third largest export crop, producing 13% of the world's canola oil. However, blackleg disease, caused by the fungus Leptospheria maculans leads to annual yield losses of 15%, with 100% loss associated with breakdown of resistance. International investment has provided novel genome resources for Brassica and L. maculans. Applying these resources to understand the co-ev ....Co-evolution of the host pathogen interaction between Leptosphaeria maculans and Brassica species. Brassica canola is Australia's third largest export crop, producing 13% of the world's canola oil. However, blackleg disease, caused by the fungus Leptospheria maculans leads to annual yield losses of 15%, with 100% loss associated with breakdown of resistance. International investment has provided novel genome resources for Brassica and L. maculans. Applying these resources to understand the co-evolution of this plant-fungal interaction could prevent the current boom-bust cycle of canola production in Australia. This study will also provide a model and knowledge base for applications in other species, leading to enhanced crops with increased plant protection and robust, reliable productivity.Read moreRead less
Genetic Basis of Variable Expression of Glycan Xeno-Autoantigens by Cattle. Meat and dairy products from cattle contain sugar structures (glycans) that are not made by humans. These structures can be recognised by the immune system and lead to allergic reactions, inflammation and potentially cancer. These non-human structures are called xeno-autoantigens or XAs. We have discovered individual cattle that do not produce one of these XAs. We will study the gene required to make XA in the XA-free ca ....Genetic Basis of Variable Expression of Glycan Xeno-Autoantigens by Cattle. Meat and dairy products from cattle contain sugar structures (glycans) that are not made by humans. These structures can be recognised by the immune system and lead to allergic reactions, inflammation and potentially cancer. These non-human structures are called xeno-autoantigens or XAs. We have discovered individual cattle that do not produce one of these XAs. We will study the gene required to make XA in the XA-free cattle to find the underlying mutation. The same approach will be used to look for natural XA-free individuals in other food species. This knowledge may enable us to create a test to facilitate the natural breeding of non-GMO, XA-free livestock to benefit Australian primary producers and provide safer food for consumers.Read moreRead less
Developing biogeographic know-how: Improving species divergence and dispersal estimations to examine geological and climatic evolutionary drivers. Anthropogenic activity over the last 150 years is now dramatically changing our global climate and ecosystems. The impact on biodiversity is already evident, and large-scale floral and faunal extinctions are predicted. This study unites a cohort of international experts in an interdisciplinary team to develop new molecular and mathematical methods to ....Developing biogeographic know-how: Improving species divergence and dispersal estimations to examine geological and climatic evolutionary drivers. Anthropogenic activity over the last 150 years is now dramatically changing our global climate and ecosystems. The impact on biodiversity is already evident, and large-scale floral and faunal extinctions are predicted. This study unites a cohort of international experts in an interdisciplinary team to develop new molecular and mathematical methods to expand our fundamental knowledge on how geological and global climate change have affected our world's species components and ecosystems in the past. This research is of environmental significance and global importance as it will improve our ability to predict how species behave under future predicted climate scenarios.Read moreRead less
Rnomics - The Role of Introns and Other Noncoding RNAs in the Evolution and Development of Complex Organisms. Approximately 98% of the transcriptional output of the human genome is noncoding RNA. The aims of the project are to (a) provide direct evidence that introns contain functional information and are part of an RNA-based regulatory network, (b) identify large numbers of new noncoding RNAs and substantiate the conclusion that noncoding RNAs genes are common in eukaryotic genomes, and (c) pr ....Rnomics - The Role of Introns and Other Noncoding RNAs in the Evolution and Development of Complex Organisms. Approximately 98% of the transcriptional output of the human genome is noncoding RNA. The aims of the project are to (a) provide direct evidence that introns contain functional information and are part of an RNA-based regulatory network, (b) identify large numbers of new noncoding RNAs and substantiate the conclusion that noncoding RNAs genes are common in eukaryotic genomes, and (c) provide supporting evidence that the higher eukaryotes have evolved a second tier of gene expression based on RNA. The project has the capacity to transform our understanding of genetic programming in the higher organisms, with considerable scientific and practical implications.Read moreRead less
The essence of being an animal: sponge allorecognition and the evolution of individuality. The human genome encodes the ability to recognise self from nonself at the cellular level. In medicine, this innate ability results in the rejection of transplanted (grafted) tissues from unrelated individuals. This project seeks to get to the evolutionary foundation of self-nonself recognition by studying this process in a simple and tractable model - a sponge from the Great Barrier Reef. Like humans, spo ....The essence of being an animal: sponge allorecognition and the evolution of individuality. The human genome encodes the ability to recognise self from nonself at the cellular level. In medicine, this innate ability results in the rejection of transplanted (grafted) tissues from unrelated individuals. This project seeks to get to the evolutionary foundation of self-nonself recognition by studying this process in a simple and tractable model - a sponge from the Great Barrier Reef. Like humans, sponges reject cells and tissues derived from another individual. By defining the genetic basis of self-recognition in sponges we reveal the antiquity of this system and the core features of histocompatibility and immunity. Such insights can inform a range of regenerative medical pursuits.Read moreRead less