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
Heads or tails - which did echinoderms lose in the evolution of radial symmetry? Echinoderms, despite their unusual radial body plan, are closely related to chordates, but it is not known how this plan evolved. This project uses gene expression studies with uniquely suited Australian species to identify genes involved in radial body plan development and generate insights into origins of chordates and the vertebrate central nervous system (CNS).
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
Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions ba ....Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions based on an individual's genetic information. In the broader community, knowledge of genes which contribute to the normal and healthy functioning of the cardiac and musculoskeletal systems will be invaluable in understanding and preventing breakdowns in these body systems.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
Controlling the first step of differentiation of embryonic cells. This project aims to improve understanding of how diverse cell types are generated for building the body plan of the embryo. The first step of embryonic cell lineage differentiation takes place at early gastrulation when the multipotent embryonic cells acquire the attributes of specific tissue lineages. This project intends to elucidate how inductive signals and gene function are integrated to drive the lineage choice of the naïve ....Controlling the first step of differentiation of embryonic cells. This project aims to improve understanding of how diverse cell types are generated for building the body plan of the embryo. The first step of embryonic cell lineage differentiation takes place at early gastrulation when the multipotent embryonic cells acquire the attributes of specific tissue lineages. This project intends to elucidate how inductive signals and gene function are integrated to drive the lineage choice of the naïve cells, by tracking the impact of the activity of signalling pathways and gene regulation on cell differentiation. This may deliver insights into the temporal hierarchy and functional attributes of the molecular switches that control stem cell differentiation. Expected outcomes may have applications in tissue engineering.Read moreRead less
A molecular paradigm of organ formation during embryonic development: the role of RhoGTPase. How do cells in the embryo acquire the correct shape and structure to form tissues and organs? This project will reveal the genes and proteins required for the formation of the early gut and associated organs and will enhance our understanding of how organs are constructed from the building blocks in the embryo.
Discovery Early Career Researcher Award - Grant ID: DE160100755
Funder
Australian Research Council
Funding Amount
$371,000.00
Summary
Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. Th ....Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. The project involves comparisons of the 3D structure of genomes in divergent species. These findings are expected to inform the underlying principles of gene regulation in animals and species evolution.Read moreRead less
Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover th ....Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover the molecular, genomic, and proteomic regulators or telomere privilege; determine the breath of telomere privilege in stem cell lineages; elucidate the functional significance of telomere privilege; and exploit telomere privilege to study fundamental biology related to telomeres and the DNA damage response.Read moreRead less
Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general ....Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general population.Read moreRead less