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
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
Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic m ....Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic mutation in individual plants, providing an unprecedented level of detail into an important but understudied source of biological variation. By applying these methods to an iconic experimental population, This project aims to provide the first insights into the genome-wide causes and consequences of somatic mutation in plants.Read moreRead less
Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity with ....Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity within a venom, and we have developed genomic tools to study the venom “dark matter”. This work will lead to the full molecular characterisation of venom biodiversity, and new venom components will be useful for research or as novel medicines.Read moreRead less
Humane Chemical Methods for Population Management of Highly Valued Large Mammals. In many countries valued wild and feral animals are nonetheless too numerous. Their population numbers must be controlled through fertility. Examples are koalas in Australia, deer and seals in North America, cattle in India and dogs in Thailand. We aim to develop benign implants for castration based upon the gonadotrophin releasing hormone (GnRH). These implants are easily administered. The outcomes will be to ....Humane Chemical Methods for Population Management of Highly Valued Large Mammals. In many countries valued wild and feral animals are nonetheless too numerous. Their population numbers must be controlled through fertility. Examples are koalas in Australia, deer and seals in North America, cattle in India and dogs in Thailand. We aim to develop benign implants for castration based upon the gonadotrophin releasing hormone (GnRH). These implants are easily administered. The outcomes will be to protect Australia's ?green? image , worldwide market opportunities for the Australian companies involved in this application and valuable intellectual property for Macquarie. The methodology will in time allow us to apply it to the treatment of cancer.Read moreRead less
Genomic Basis of Resistance to Poisoning by Sodium Fluoroacetate (Compound 1080) in Australian Wildlife. In Australia agricultural conservation activities worth billions of dollars are protected by using sodium fluoroacetate (1080) against pest animals. Target species are Australian rabbits and foxes and New Zealand brushtail possums. Prolonged use of biocontrol agents causes genetic resistance. This occurs naturally in Western Australia in native animals living in areas with high levels of 1080 ....Genomic Basis of Resistance to Poisoning by Sodium Fluoroacetate (Compound 1080) in Australian Wildlife. In Australia agricultural conservation activities worth billions of dollars are protected by using sodium fluoroacetate (1080) against pest animals. Target species are Australian rabbits and foxes and New Zealand brushtail possums. Prolonged use of biocontrol agents causes genetic resistance. This occurs naturally in Western Australia in native animals living in areas with high levels of 1080 in native plants. As part of the Kangaroo Genome project our aim is to discover the genomic basis of this resistance. The outcomes will be improved ability to manage pest animal populations and understanding of the evolution of plant-animal interactions.Read moreRead less
New phylogenetic approaches for understanding evolution at the genome scale. This project aims to use genome data to improve our understanding of the evolutionary process, including the forces that shape evolution on a whole-genome scale. The project plans to create a curated database of genome sequences and a comprehensive framework for evolutionary analyses of genomes. The new approach is designed to be used to analyse patterns of evolutionary rate variation to identify the key features of gen ....New phylogenetic approaches for understanding evolution at the genome scale. This project aims to use genome data to improve our understanding of the evolutionary process, including the forces that shape evolution on a whole-genome scale. The project plans to create a curated database of genome sequences and a comprehensive framework for evolutionary analyses of genomes. The new approach is designed to be used to analyse patterns of evolutionary rate variation to identify the key features of genome evolution. In addition, the development of a genome-scale approach to molecular dating will improve estimates of the timescale of the Tree of Life. This project is expected to yield useful insights into molecular evolution and to provide a valuable guide for future evolutionary analyses of genomes.Read moreRead less
Testing links between genomic and morphological evolutionary rates. This project aims to identify, understand, and characterise patterns of evolutionary rates across different levels of biological variation. The project expects to generate knowledge about the tempo and mode of evolution by using a phylogenetic approach to test fundamental models of evolutionary rates, including the link between rates of genomic and morphological evolution. Expected outcomes of this project include detailed insig ....Testing links between genomic and morphological evolutionary rates. This project aims to identify, understand, and characterise patterns of evolutionary rates across different levels of biological variation. The project expects to generate knowledge about the tempo and mode of evolution by using a phylogenetic approach to test fundamental models of evolutionary rates, including the link between rates of genomic and morphological evolution. Expected outcomes of this project include detailed insights into the tempo and mode of macroevolution, better modelling of genomic and phenotypic evolution, and improved design of studies in evolutionary genomics. Benefits of the project include greater understanding of the evolutionary processes that have generated the diversity of the Australian biota.Read moreRead less
Directed evolution of ancestral bacterial flagellar motors. This project aims to produce new knowledge concerning the adaptation of bacterial species to wide environmental changes. The bacterial flagellar motor (BFM) is a motor 40 nanometers in diameter that builds itself into bacterial membranes, rotates five times faster than a Formula One engine, and switches directions in milliseconds. . This project will combine ancestral reconstruction of ancient motor components with protein engineering t ....Directed evolution of ancestral bacterial flagellar motors. This project aims to produce new knowledge concerning the adaptation of bacterial species to wide environmental changes. The bacterial flagellar motor (BFM) is a motor 40 nanometers in diameter that builds itself into bacterial membranes, rotates five times faster than a Formula One engine, and switches directions in milliseconds. . This project will combine ancestral reconstruction of ancient motor components with protein engineering to understand how the different ion channels that power the BFM in different species are selective for different positive ions. It will inspire and inform future manufacturing in bionanotechnology.Read moreRead less
Estimating evolutionary time-scales using genomic sequence data: exploiting opportunities and meeting challenges. Genomic data are being produced at a phenomenal rate, enabling detailed investigations of various biological questions. This project will exploit the new opportunities for improving the estimation of evolutionary time-scales, and develop methods and software to address the new challenges that have surfaced.