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
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
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
Pseudo grains and adaptiveness in the Eastern Himalayas. Providing enough food for a growing planet and changing is one of the key challenges humanity must face in coming decades. Our research aims to contribute solutions to this problem by researching the domestication history and spread of two crops that are important to the eastern Himalayas: buckwheat and job's tears. We will use ethnolinguistic methodologies to document the current uses of these crops, and then incorporate archaeological, a ....Pseudo grains and adaptiveness in the Eastern Himalayas. Providing enough food for a growing planet and changing is one of the key challenges humanity must face in coming decades. Our research aims to contribute solutions to this problem by researching the domestication history and spread of two crops that are important to the eastern Himalayas: buckwheat and job's tears. We will use ethnolinguistic methodologies to document the current uses of these crops, and then incorporate archaeological, and genetic methodologies to determine whether or not the eastern Himalayas have been centres of domestication for these crops. The outcomes will include ethnolinguistic documentation, timing of domestication, and training in the relevant indigenous communities.Read moreRead less
Global climate change and coastal landscape evolution in southern Australia. This project aims to reconstruct environmental changes that occurred in southern Australia during a geologically recent time interval termed the Early-Middle Pleistocene Transition (1.2 million to 700 thousand years ago) and an interglacial period some 400,000 years ago. Using innovative geochronological, geochemical and modelling techniques, the environmental changes that shaped modern Australian coastal landscapes, in ....Global climate change and coastal landscape evolution in southern Australia. This project aims to reconstruct environmental changes that occurred in southern Australia during a geologically recent time interval termed the Early-Middle Pleistocene Transition (1.2 million to 700 thousand years ago) and an interglacial period some 400,000 years ago. Using innovative geochronological, geochemical and modelling techniques, the environmental changes that shaped modern Australian coastal landscapes, including the intensification of aridity and their timing will be examined. The project will yield new knowledge about the sensitivity of landscapes to current and ongoing environmental changes and derive explanatory models of the rates and characteristics of landscape response to assist future coastal environmental management.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
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
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
Earth's Dynamic Topography Through Space and Time. A key component of Earth’s topography remains enigmatic. This so-called dynamic topography is transient, varying in response to convection within Earth’s mantle. This project aims to use a data-driven computational approach to: (i) reconstruct the evolution of dynamic topography over the recent geological history of our planet (Cenozoic Era, 0-66 million years ago); and (ii) uncover the mechanisms controlling its spatial and temporal evolution. ....Earth's Dynamic Topography Through Space and Time. A key component of Earth’s topography remains enigmatic. This so-called dynamic topography is transient, varying in response to convection within Earth’s mantle. This project aims to use a data-driven computational approach to: (i) reconstruct the evolution of dynamic topography over the recent geological history of our planet (Cenozoic Era, 0-66 million years ago); and (ii) uncover the mechanisms controlling its spatial and temporal evolution. This transformational new understanding will connect the evolution of our planet's surface environments to its deep interior, revealing the impact of dynamic topography on sea level change, flooding, river networks, groundwater systems, habitat development and the distribution of economic resources. Read moreRead less