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
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
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
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
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
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