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
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
Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The pr ....Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The project will provide fundamental advances in our knowledge of the nutrient transport during pregnancy that is required to produce a healthy baby.Read moreRead less
Lively reproduction: do common molecules underlie all vertebrate live birth? Most animals lay eggs, but some (most mammals, including humans and some reptiles) give birth to live young. This project will reveal the molecules underlying the evolution of live birth and fundamental processes of early pregnancy, which potentially will lead to future developments in reproductive science.
Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the verteb ....Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the vertebrate immune system and providing the basis for making immunological reagents which are necessary for studying monotreme diseases (as a precautionary conservation strategy).Read moreRead less
Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new ....Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new knowledge about the unique biology of Australia's marsupial fauna.This project will provide significant benefits, including enhanced capacity for reproduction research in Australia, new international collaborations between Melbourne and Yale, and a new explanation for the puzzling role of inflammation in pregnancy.Read moreRead less
High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. Wit ....High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. With this new technology we aim to identify DNA polymerases with improved performance that benefit biotechnological applications. Additionally, these single-molecule directed-evolution methods will benefit the wider scientific community and lay the foundation for further advances in directed evolution.Read moreRead less
Life and times of Beringian biota from luminescence and radiocarbon dating of sedimentary DNA: chronologies for palaeoenvironmental and archaeological archives. This study will yield important new data on the time of entry of humans into a previously uninhabited continent (North America) and the record of subsequent human-environment interactions. The same broad issues apply to Australia, so understanding the sequence and causes of events in Beringia will provide insights into human disruption o ....Life and times of Beringian biota from luminescence and radiocarbon dating of sedimentary DNA: chronologies for palaeoenvironmental and archaeological archives. This study will yield important new data on the time of entry of humans into a previously uninhabited continent (North America) and the record of subsequent human-environment interactions. The same broad issues apply to Australia, so understanding the sequence and causes of events in Beringia will provide insights into human disruption of the Australian ecosystem. The development of improved techniques in palaeogenetics and geochronology will benefit researchers worldwide, increase the capacity for commercial services, and enhance Australia's international standing in cutting edge science. We will train high-quality graduate students and create new collaborative initiatives and opportunities for research, exchange, training and education.Read moreRead less
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less
Pleistocene evolutionary dynamics and past environments of Siberia: Reconstructions using luminescence dating of ancient DNA sedimentary archives. This study will yield critical new insights into faunal-environment interactions in Siberia and their long-term implications for the evolution and extinction of Siberia's biota. These fundamental issues are of relevance to Australian archaeology, palaeontology and biogeography, and so our discoveries are of direct interest to Australian researchers st ....Pleistocene evolutionary dynamics and past environments of Siberia: Reconstructions using luminescence dating of ancient DNA sedimentary archives. This study will yield critical new insights into faunal-environment interactions in Siberia and their long-term implications for the evolution and extinction of Siberia's biota. These fundamental issues are of relevance to Australian archaeology, palaeontology and biogeography, and so our discoveries are of direct interest to Australian researchers studying these disciplines. The methodological advancements in OSL dating and DNA techniques that will accompany this research will enhance Australia's international scientific standing and create new opportunities for collaborative initiatives in both cutting-edge scientific research and consulting activities.Read moreRead less