Lungfish Paired Fins and the Origin of Limbs as an Evolutionary Novelty. This project will utilise a uniquely Australian animal, the lungfish, to address a hitherto unresolved problem of considerable scientific significance - how a fish fin evolved into a tetrapod (four-legged animal) limb. The Australian lungfish is the most primitive of the four surviving genera of lobe-finned fish and is recognised as the closest living ancestor to the tetrapods. It is listed as 'vulnerable' in its native ha ....Lungfish Paired Fins and the Origin of Limbs as an Evolutionary Novelty. This project will utilise a uniquely Australian animal, the lungfish, to address a hitherto unresolved problem of considerable scientific significance - how a fish fin evolved into a tetrapod (four-legged animal) limb. The Australian lungfish is the most primitive of the four surviving genera of lobe-finned fish and is recognised as the closest living ancestor to the tetrapods. It is listed as 'vulnerable' in its native habitat. Macquarie University, however, has the only captive breeding population of lungfish in the world. We are thus uniquely placed to address critically important questions concerning the evolution of fish into tetrapods. Read moreRead less
Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood for ....Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood formation will be studied. We will establish techniques for several steps that will be useful for all zebrafish mapping projects. We expect the genetic characterization of these mutants to provide new insights into nerve cell survival, gut development, and blood formation.Read moreRead less
Neurogenesis in bilateral larval and radial adult body plans: identification of echinoderm homologues of the chordate central nervous system. The modern synthesis of embryology and gene expression studies, as undertaken in this project with sea stars, is a major way forward to achieve advances in our understanding of animal evolution and generate new insights into the mystery that surrounds the origin of our own phylum, the Chordata. This project utilises life history diversity in species that a ....Neurogenesis in bilateral larval and radial adult body plans: identification of echinoderm homologues of the chordate central nervous system. The modern synthesis of embryology and gene expression studies, as undertaken in this project with sea stars, is a major way forward to achieve advances in our understanding of animal evolution and generate new insights into the mystery that surrounds the origin of our own phylum, the Chordata. This project utilises life history diversity in species that are unique Australian fauna. Extreme life history diversity as seen in these sea stars is unparalleled on a global scale and provides an important resource to generate new discoveries on the processes underlying evolution in the sea and enhance our understanding of marine systems. 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.
Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the form ....Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the formulation of new research hypotheses, enriching the curriculum and the provision of informed counselling. The embryological expertise developed for this project will enhance the nation's research capability through the sharing of skills and knowledge with a national network of academic and industrial research teams. Read moreRead less
microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried m ....microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried method, and to explore bioinformatics-based methods of identification. We will also study the expression of miRNAs in mouse embryos at successive stages, and develop a microarray assay for miRNA expression.Read moreRead less
Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardi ....Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardiac pathways for a better understanding of heart formation and disease, and to develop advanced techniques that will contribute to strengthen Australian basic and strategic research.Read moreRead less
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
Capturing tissue-specific progenitors from embryos and stem cells. This project aims to delineate the precursor cells in the embryo that give rise specifically to major cell types in the body. The project will use genetic analysis to elucidate the critical genetic activity that underpins the genesis of these precursor cells and to track the trajectory and the scope of cell differentiation. The embryological knowledge will provide insights into the fundamentals of developmental process for gener ....Capturing tissue-specific progenitors from embryos and stem cells. This project aims to delineate the precursor cells in the embryo that give rise specifically to major cell types in the body. The project will use genetic analysis to elucidate the critical genetic activity that underpins the genesis of these precursor cells and to track the trajectory and the scope of cell differentiation. The embryological knowledge will provide insights into the fundamentals of developmental process for generating cellular diversity and enable identifying unique precursors and the evaluation of the efficacy of deriving the biological relevant cell types from the stem cells. This project expects to have a significant impact on the translation to cell production methodology for tissue engineering and bioreactor technology.Read moreRead less