Investigating a new way in which diet impacts animal biology. This project aims to investigate the importance of a new way in which diet can alter animal biology. High fat or high sugar diets increase the binding of products of metabolism to chromosomes, which can completely alter the way that DNA is packaged and read. This project will use cell culture, rodent and fly models to identify the regions of the genome that are most affected by the new process. The project will also determine whether ....Investigating a new way in which diet impacts animal biology. This project aims to investigate the importance of a new way in which diet can alter animal biology. High fat or high sugar diets increase the binding of products of metabolism to chromosomes, which can completely alter the way that DNA is packaged and read. This project will use cell culture, rodent and fly models to identify the regions of the genome that are most affected by the new process. The project will also determine whether the cell is harmed, or in fact harnesses the process to control development or metabolism. This project has implications for our understanding of the ways in which genes interact with the environment especially in times of change.Read moreRead less
Demographic and evolutionary inferences from large, whole-genome datasets. A new data structure for genome-wide datasets has allowed great improvements in the efficiency of genomic data storage and in population genomics simulations, which are crucial to developing and testing mathematical models of population history and species evolution. We will take these advances in new directions, using efficient data structures to dramatically improve inferences about: the demographic histories of popul .... Demographic and evolutionary inferences from large, whole-genome datasets. A new data structure for genome-wide datasets has allowed great improvements in the efficiency of genomic data storage and in population genomics simulations, which are crucial to developing and testing mathematical models of population history and species evolution. We will take these advances in new directions, using efficient data structures to dramatically improve inferences about: the demographic histories of populations, rates of genome change, and phylogenetic networks, and we will develop the first inference methods for the multispecies coalescent with recombination. Outcomes will include advances in understanding the evolutionary histories of humans and other species, including pathogens of importance for global health.Read moreRead less
The control of cell signalling by membrane remodelling. Cells secrete signalling molecules called growth factors to drive critical developmental processes such as growth, differentiation and death. This project aims to understand a new mechanism that we have discovered for the control of growth factors by a protein family evolved to damage cell membranes. This is highly novel since the usual role of these proteins is to kill pathogens targeted by the immune system. By coupling innovative genetic ....The control of cell signalling by membrane remodelling. Cells secrete signalling molecules called growth factors to drive critical developmental processes such as growth, differentiation and death. This project aims to understand a new mechanism that we have discovered for the control of growth factors by a protein family evolved to damage cell membranes. This is highly novel since the usual role of these proteins is to kill pathogens targeted by the immune system. By coupling innovative genetics, high-resolution imaging, and advanced biochemical analyses, this project intends to provide key molecular insights into how cell signalling can be regulated during animal development. We anticipate that this will impact our general understanding of membrane biology and its influence on cell signalling.Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.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
Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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The transgenerational effect of thermosensing in plants. This project aims to understand how thermosensing mechanisms in plants result in transgenerational change, and potentially adaptation to climate. Exploiting the recent discovery of the thermosensor phytochrome B, this project will decipher the molecular cascade which, either through long-distance communication or through persistence of an epigenetic state in the cell lineage, could lead to a trans generational memory in plants helping with ....The transgenerational effect of thermosensing in plants. This project aims to understand how thermosensing mechanisms in plants result in transgenerational change, and potentially adaptation to climate. Exploiting the recent discovery of the thermosensor phytochrome B, this project will decipher the molecular cascade which, either through long-distance communication or through persistence of an epigenetic state in the cell lineage, could lead to a trans generational memory in plants helping with climate adaptation. This project will unravel novel molecular mechanisms, which have the potential to pave the way for designing new climate-proofing solutions to cope with temperature uncertainty.Read moreRead less
New insights into female reproductive tract formation and tubulogenesis. Aims: This project aims to improve our understanding of female reproductive tract formation by studying its developmental origins. Most of the female reproductive tract derives from a pair of embryonic tubes called Müllerian ducts, the formation of which is incompletely understood. Significance: Using chicken and mouse models and innovative genetic approaches, the project will undercover novel genes and cellular pathways in ....New insights into female reproductive tract formation and tubulogenesis. Aims: This project aims to improve our understanding of female reproductive tract formation by studying its developmental origins. Most of the female reproductive tract derives from a pair of embryonic tubes called Müllerian ducts, the formation of which is incompletely understood. Significance: Using chicken and mouse models and innovative genetic approaches, the project will undercover novel genes and cellular pathways in Müllerian duct formation. Expected outcomes: This work will enhance knowledge in the biological sciences, in the area of female reproduction and how tubes form in biological systems. Benefits: It will train research scientists, develop collaborations and enhance Australia’s high standing in the field of reproduction.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
Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cel ....Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cell movement in mammalian organ formation and develop advanced cell segmentation and tracking methods for use in the scientific community. We anticipate this project will generate fundamental insights into how cells interact to build complex organs.Read moreRead less