The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained perso ....The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained personnel in genomics and neuroscience. This should deliver many benefits, including a better understanding of how the brain forms, training of higher degree by research students, as well as tools and methods of benefit to the academic research and biotechnology sectors.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
Investigating a novel factor impacting stem cell development. This project aims to investigate how stem cells are controlled during animal development, by exploring how a specific protein, essential for embryonic development, controls cell fate decisions during the early stages of life. This project expects to generate new knowledge in stem cell biology, embryonic development, and general mechanisms controlling cell fates, using innovative approaches in gene editing and high-throughput imaging. ....Investigating a novel factor impacting stem cell development. This project aims to investigate how stem cells are controlled during animal development, by exploring how a specific protein, essential for embryonic development, controls cell fate decisions during the early stages of life. This project expects to generate new knowledge in stem cell biology, embryonic development, and general mechanisms controlling cell fates, using innovative approaches in gene editing and high-throughput imaging. Expected outcomes of this project include enhanced capacity for fundamental stem cell biology in Australia. This should provide significant benefits, such as training of young Australian researchers in frontier technologies, and new knowledge in fundamental aspects of life, including embryonic development.Read moreRead less
Neurovascular pericytes in development and brain regeneration. The brain is responsible for a quarter of the body’s metabolism and is thus perfused by an extensive network of blood vessels. Pericytes surround these vessels and interact with neurons, glia, immune cells and neural stem cells of the neurovascular unit. Pericytes influence brain development, function and regeneration but remain enigmatic. This project investigates molecular control of pericyte development, functional coupling of per ....Neurovascular pericytes in development and brain regeneration. The brain is responsible for a quarter of the body’s metabolism and is thus perfused by an extensive network of blood vessels. Pericytes surround these vessels and interact with neurons, glia, immune cells and neural stem cells of the neurovascular unit. Pericytes influence brain development, function and regeneration but remain enigmatic. This project investigates molecular control of pericyte development, functional coupling of pericytes with adjacent cells and pericyte function in tissue regeneration. We aim to produce new fundamental knowledge in brain development, structure, function and evolution. New knowledge generated here may lead to future approaches in stem cell biology, tissue engineering, regeneration and ageing of the brain. Read moreRead less
Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will gene ....Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will generate basic scientific knowledge and new intellectual property that will afford new opportunities for research and development. The outcomes of this project will help to devise strategies to treat diseases such as autoimmunity, cancer and metabolic syndrome, and will thus benefit veterinary and human health.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
Genetic regulation of avian sex determination. This project aims to enhance our understanding of gonadal sex determination (testis versus ovary development), using innovative genetic approaches that exploit the avian embryo as a model system. The project aims to define the key molecular events regulating gonadal sex determination in birds. It intends to enhance knowledge in the area of cell biology, embryology, and sex determination specifically. Importantly, it will have application to the poul ....Genetic regulation of avian sex determination. This project aims to enhance our understanding of gonadal sex determination (testis versus ovary development), using innovative genetic approaches that exploit the avian embryo as a model system. The project aims to define the key molecular events regulating gonadal sex determination in birds. It intends to enhance knowledge in the area of cell biology, embryology, and sex determination specifically. Importantly, it will have application to the poultry industry. Currently, half of all hatchlings (the undesired sex) are culled. The proposed project intends to illuminate those genetic pathways that can be targeted to produce single-sex lines of birds, a major goal of the multi-billion dollar Australian and global poultry industries.Read moreRead less
Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model t ....Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model to generate new knowledge of the cellular and genetic components that drive evolution of different brain parts and shapes the vertebrate brain. In doing so the project aims to provide research training, excellence and knowledge that in future may benefit health and the society. 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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Predicting adaptation and range expansion under climate change. This project investigates the repeatability and thereby the predictability of adaptation to climate change by leveraging 1000 genomes sampled over 150 years and multiple climatic gradients in the rapidly adapting, globally invasive, and highly allergenic ragweed. We expect to deepen our understanding of the genetic basis of adaptation and decipher the circumstances under which adaptive genetic change is repeatable, by integrating a ....Predicting adaptation and range expansion under climate change. This project investigates the repeatability and thereby the predictability of adaptation to climate change by leveraging 1000 genomes sampled over 150 years and multiple climatic gradients in the rapidly adapting, globally invasive, and highly allergenic ragweed. We expect to deepen our understanding of the genetic basis of adaptation and decipher the circumstances under which adaptive genetic change is repeatable, by integrating a novel evolutionary model with genomic data. We will develop the capacity to predict species’ distributions and trait evolution under climate change using a powerful empirical dataset. This will provide us with the capacity to anticipate and manage the effects of climate change on noxious and threatened species.Read moreRead less