The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this projec ....The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this project include uncovering the anatomical changes underpinning the origin of the vertebrate appendicular system. This should provide significant benefits as it will inform our own natural history and provide a paradigm for studying gene network
conservation, phylogenetic modifications, and the acquisition of novel structures.Read moreRead less
Ancestral, conserved and novel mechanisms in marsupial genomic imprinting. Genomic imprinting is the differential expression pattern of some genes depending on whether the gene copy came from the mother or the father. This differential expression is essential for embryonic development and errors lead to disease. To date, most of our knowledge of the control of genomic imprinting comes from the mouse, but much less is known about this process in marsupials. Our comparative approach, using marsupi ....Ancestral, conserved and novel mechanisms in marsupial genomic imprinting. Genomic imprinting is the differential expression pattern of some genes depending on whether the gene copy came from the mother or the father. This differential expression is essential for embryonic development and errors lead to disease. To date, most of our knowledge of the control of genomic imprinting comes from the mouse, but much less is known about this process in marsupials. Our comparative approach, using marsupial mammals that are distantly related to mice and humans, aims to clarify how genomic imprinting mechanisms have evolved, which patterns are conserved across mammals, and which vary. Our proposed research aims to provide new approaches and understanding of this fundamental process essential for the continuation of life.
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Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to und ....Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to understanding how new mutations arise in sperm and potentially affect offspring phenotype, adaptation and evolution. As chemicals, drugs and diet can affect epigenetic function, our studies will also contribute to determining how epigenetic inheritance affects environmental, agricultural and healthcare outcomes.Read moreRead less
Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study ....Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study is important to every biological process in plants and animals driven by a change in gene expression. Expected Outcomes: This study will increase our biological knowledge in transcription control. Benefit: The knowledge gained has future applications in genomics and broad implications for biotechnology and industry.Read moreRead less
The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemi ....The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemical modifications impact cell specific gene nuclear positioning and how this regulates changes in gene expression associated with immune cell activation. An outcome will be identification of novel molecular mechanisms that will have broad applicability across cellular biology, and provide novel targets for drug development.Read moreRead less
Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.Read moreRead less
Histone H3.3-dependent transcriptional control and B cell differentiation. This project aims to investigate the fundamental way cells assemble transcriptional machinery to turn on genes and retain transcriptional memory. This project expects to generate new knowledge in the areas of both chromatin biology and immunology, using interdisciplinary approaches. Expected outcomes of this project include an enhanced capacity, through institutional and international collaborations, to determine whether ....Histone H3.3-dependent transcriptional control and B cell differentiation. This project aims to investigate the fundamental way cells assemble transcriptional machinery to turn on genes and retain transcriptional memory. This project expects to generate new knowledge in the areas of both chromatin biology and immunology, using interdisciplinary approaches. Expected outcomes of this project include an enhanced capacity, through institutional and international collaborations, to determine whether the rapid transcription and function characteristic of immune memory in response to stimuli is due to histone H3 variant and its associated nuclear bodies. This should provide significant benefits, such as understanding epigenetic mechanisms that underlie transcription initiation and maintenance across many species.Read moreRead less
Genetic, Cellular and Molecular Analysis of Cardiac Ventricular Septation. The project aims to define the blueprint for ventricular septation in the mammalian heart – how, during heart development, a single ventricle becomes divided in two by a muscular wall, thus creating left and right pumps and electrical circuits serving the body and lung circulations separately. A proprietary mouse genetic model was created and will be used to probe the cellular and molecular mechanisms of septation using n ....Genetic, Cellular and Molecular Analysis of Cardiac Ventricular Septation. The project aims to define the blueprint for ventricular septation in the mammalian heart – how, during heart development, a single ventricle becomes divided in two by a muscular wall, thus creating left and right pumps and electrical circuits serving the body and lung circulations separately. A proprietary mouse genetic model was created and will be used to probe the cellular and molecular mechanisms of septation using new technologies able to resolve biology at a single-cell level. Outcomes may include new knowledge on heart development and evolution, including how the cardiac electrical system is formed, and how cell boundaries and tissue complexity are generated. The project may advance new technologies and create new data resources.Read moreRead less
Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this pro ....Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this project aims to combine anthropological genetics with cutting-edge functional genomics in a pioneer multidisciplinary approach. Ultimately, this project may transform our understanding of both the population and evolutionary pressures that have acted upon these groups in the past 50,000 years.Read moreRead less
Fins to Limbs: Investigating the Evolution of complex Limb Musculature. This application aims to investigates the basis of the fin-to-limb transition, an event that set the stage for the entire tetrapod radiation. This project expects to generate new knowledge concerning the natural history of vertebrates using a multidisciplinary approach that combines paleontology and embryology of unique Australian fauna. While the skeletal changes associated with the move from water to land have been investi ....Fins to Limbs: Investigating the Evolution of complex Limb Musculature. This application aims to investigates the basis of the fin-to-limb transition, an event that set the stage for the entire tetrapod radiation. This project expects to generate new knowledge concerning the natural history of vertebrates using a multidisciplinary approach that combines paleontology and embryology of unique Australian fauna. While the skeletal changes associated with the move from water to land have been investigated, little is known about the origin of tetrapod limb muscles. This proposal has as an expected outcome, a determination of how limb muscles arose during evolution. This knowledge should provide significant benefits by transforming our understanding of the origins of the tetrapod body plan and our own natural history.Read moreRead less