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
Origin and evolution of animal-bacterial symbiosis. This project seeks to understand how interactions between animals and their microbial symbionts – the holobiont – evolved, and how they are influenced by the environment over an animal's life. Using a homegrown Australian model, a sea sponge from the Great Barrier Reef, and advanced multi-omic approaches (genomics plus cell biology), this project aims to uncover the mechanisms underlying the establishment and maintenance of the holobiont throug ....Origin and evolution of animal-bacterial symbiosis. This project seeks to understand how interactions between animals and their microbial symbionts – the holobiont – evolved, and how they are influenced by the environment over an animal's life. Using a homegrown Australian model, a sea sponge from the Great Barrier Reef, and advanced multi-omic approaches (genomics plus cell biology), this project aims to uncover the mechanisms underlying the establishment and maintenance of the holobiont through development, and under changing ecological and environmental conditions. Because of the evolutionary position of sponges, outcomes of this project expect to reveal cardinal rules governing animal-microbe interactions that are fundamental to the health and conservation of most animals and ecosystems.Read moreRead less
Fins to Limbs: Investigating the Evolution of complex Limb Musculature. This application aims to investigates the basis of the fin-to-limb transition, an event that set the stage for the entire tetrapod radiation. This project expects to generate new knowledge concerning the natural history of vertebrates using a multidisciplinary approach that combines paleontology and embryology of unique Australian fauna. While the skeletal changes associated with the move from water to land have been investi ....Fins to Limbs: Investigating the Evolution of complex Limb Musculature. This application aims to investigates the basis of the fin-to-limb transition, an event that set the stage for the entire tetrapod radiation. This project expects to generate new knowledge concerning the natural history of vertebrates using a multidisciplinary approach that combines paleontology and embryology of unique Australian fauna. While the skeletal changes associated with the move from water to land have been investigated, little is known about the origin of tetrapod limb muscles. This proposal has as an expected outcome, a determination of how limb muscles arose during evolution. This knowledge should provide significant benefits by transforming our understanding of the origins of the tetrapod body plan and our own natural history.Read moreRead less
Evolution of environmental regulation of cell states in animal life cycles. This project seeks to understand how the environment influences the fate of cells over an animal's life, and how this influence originated in animal evolution. Using a homegrown Australian model, a sea sponge from the Great Barrier Reef, and advanced multi-omic approaches (genomics plus cell biology), this project aims to uncover the mechanisms underlying global cell state changes that are induced through the interplay o ....Evolution of environmental regulation of cell states in animal life cycles. This project seeks to understand how the environment influences the fate of cells over an animal's life, and how this influence originated in animal evolution. Using a homegrown Australian model, a sea sponge from the Great Barrier Reef, and advanced multi-omic approaches (genomics plus cell biology), this project aims to uncover the mechanisms underlying global cell state changes that are induced through the interplay of environmental and endogenous signals at metamorphosis. Because of the evolutionary position of sponges, outcomes of this project expect to reveal the cardinal rules governing environmentally-induced cell state changes that are obligatory for most animals to complete their complex life cycles.Read moreRead less
How does embryonic physiology shape the divergence of brain development? . Unlike placental mammals (humans, mice, dogs etc) marsupials give birth to very immature young that finalise development in the pouch. Despite this remarkable distinction in the major mammalian lineages, very little is known about how differing reproductive environments impact development and evolution. This project aims to explore how developing inside or outside a uterus impacts brain development in placental vs marsupi ....How does embryonic physiology shape the divergence of brain development? . Unlike placental mammals (humans, mice, dogs etc) marsupials give birth to very immature young that finalise development in the pouch. Despite this remarkable distinction in the major mammalian lineages, very little is known about how differing reproductive environments impact development and evolution. This project aims to explore how developing inside or outside a uterus impacts brain development in placental vs marsupial mammals. Expected outcomes include expanding theories of how different body systems are connected in development and evolution, understanding what aspects of marsupial development might be especially sensitive to variations in environment brought about by climate change and enhancing Australia’s research capabilities.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
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
A Universal Power Law for Growth and Diversity of Dinosaur and Bird Beaks. Universal rules that govern how animals grow have tremendous power to explain the highly complex processes of growth and development. The project investigators have recently discovered a new rule of growth that controls how teeth, horns, claws and beaks are generated in animals. This project aims to use this new rule to examine the evolution and diversity of beaks in birds and dinosaurs. By combining 3D modelling, biomech ....A Universal Power Law for Growth and Diversity of Dinosaur and Bird Beaks. Universal rules that govern how animals grow have tremendous power to explain the highly complex processes of growth and development. The project investigators have recently discovered a new rule of growth that controls how teeth, horns, claws and beaks are generated in animals. This project aims to use this new rule to examine the evolution and diversity of beaks in birds and dinosaurs. By combining 3D modelling, biomechanics and genetic analysis of bird beak development with the study of dinosaur fossils, this project expects to reveal the underlying processes controlling the growth and evolution of beaks. The anticipated goal of this project is to show the power of new theoretical models to explain the diversity of life.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
A new universal mechanism controlling body proportions in animals. This project aims to establish that a recently-discovered mechanism, the inhibitory cascade, determines the basic proportions of appendages and body segments in a diverse range of animal groups, particularly vertebrates and arthropods. The goals of the project are to reveal the molecular mechanisms in mice and insects, and build computer simulations to show how to manipulate the control of development by the inhibitory cascade. T ....A new universal mechanism controlling body proportions in animals. This project aims to establish that a recently-discovered mechanism, the inhibitory cascade, determines the basic proportions of appendages and body segments in a diverse range of animal groups, particularly vertebrates and arthropods. The goals of the project are to reveal the molecular mechanisms in mice and insects, and build computer simulations to show how to manipulate the control of development by the inhibitory cascade. The project should benefit bioengineering by establishing control mechanisms for the manipulation and regeneration of teeth and limbs.Read moreRead less