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
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
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
Dynamic evolution of mutation rates: causes and impacts on genomic analysis. This project aims to illuminate the role of variation in mutation rate in driving evolutionary change. Mutation rate is a core parameter in evolutionary analyses in essential applications including epidemiology, conservation and medicine, yet remains a “black box” given arbitrary universal values. This project will take a whole-of-biodiversity approach to understanding the forces shaping mutation rate, impact on evoluti ....Dynamic evolution of mutation rates: causes and impacts on genomic analysis. This project aims to illuminate the role of variation in mutation rate in driving evolutionary change. Mutation rate is a core parameter in evolutionary analyses in essential applications including epidemiology, conservation and medicine, yet remains a “black box” given arbitrary universal values. This project will take a whole-of-biodiversity approach to understanding the forces shaping mutation rate, impact on evolution of biodiversity and effect on accuracy and precision of phylogenetic analyses. Using Australian case studies, the expected outcome of this project will be a greater understanding variation in mutation rate between species, providing significant benefits in developing more sophisticated and reliable phylogenetic analyses.Read moreRead less
Evolution and mechanisms of interactions in biofilm communities. This project aims to study the long-term experimental evolution of a mixed species bacterial biofilm community. This project expects to gain understanding of the genetic and physiological basis of community evolution. Expected outcomes of this project will be an understanding of how synthetic communities evolve. This will significantly benefit the use of synthetic communities relevant to fields such as antibiotic design, biotechnol ....Evolution and mechanisms of interactions in biofilm communities. This project aims to study the long-term experimental evolution of a mixed species bacterial biofilm community. This project expects to gain understanding of the genetic and physiological basis of community evolution. Expected outcomes of this project will be an understanding of how synthetic communities evolve. This will significantly benefit the use of synthetic communities relevant to fields such as antibiotic design, biotechnology, bioremediation, and synthetic biology where evolution can be inhibited or exploited, respectively.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
Mitochondria as sensors of environmental threats. This project aims to understand how energy-generating mitochondria control immune responses, both in immune cells called macrophages and in the nematode Caenorhabditis elegans (a free-living roundworm used as a model organism to study gene function and evolutionary biology). The project expects to advance knowledge of how a process called mitochondrial fission enables cells to respond to environmental threats. Expected outcomes include important ....Mitochondria as sensors of environmental threats. This project aims to understand how energy-generating mitochondria control immune responses, both in immune cells called macrophages and in the nematode Caenorhabditis elegans (a free-living roundworm used as a model organism to study gene function and evolutionary biology). The project expects to advance knowledge of how a process called mitochondrial fission enables cells to respond to environmental threats. Expected outcomes include important conceptual advances in cell biology and genetics, new international and national collaborations, and improved methods for cell biology research. Anticipated benefits include a knowledge base that can be indirectly applied in the long term in the development of new strategies to combat infections.Read moreRead less
Adaptation to life in the dark: genomic analyses of blind beetles. This project aims to utilise a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. This project focuses on the evolution of Heat Shock protein (Hsp) genes that play critical roles in adaptation to environmental stress and the process of de-canalisation, the rel ....Adaptation to life in the dark: genomic analyses of blind beetles. This project aims to utilise a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. This project focuses on the evolution of Heat Shock protein (Hsp) genes that play critical roles in adaptation to environmental stress and the process of de-canalisation, the release of cryptic genetic variation that can allow novel morphologies to evolve in new environments. The project expects to provide further understanding of how species may potentially adapt to environmental stresses in the future, including climate change.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
Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine ....Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine how evolution works at the DNA level. This proposal will determine if animals that develop identical skull shapes, also show identical changes in their DNA. The findings will define new developmental genes and explain how selection, adaptation and evolution works at the DNA level. Read moreRead less