How is the blood cell population size controlled? Macrophage-like cells are an ancient animal blood cell lineage critically important for development, immunity, and homeostasis. This fellowship seeks to reveal the genes and control mechanisms used by animals to achieve an optimally-sized army of these cells - to contain threats for survival upon infection, heal following acute stress exposures, or for development, ongoing maintenance, and repair of wear and tear. By marrying the genetic tractabi ....How is the blood cell population size controlled? Macrophage-like cells are an ancient animal blood cell lineage critically important for development, immunity, and homeostasis. This fellowship seeks to reveal the genes and control mechanisms used by animals to achieve an optimally-sized army of these cells - to contain threats for survival upon infection, heal following acute stress exposures, or for development, ongoing maintenance, and repair of wear and tear. By marrying the genetic tractability of the model organism Drosophila and its simple, yet conserved blood cell system, this project will yield new insights into the mechanisms that govern the animal blood cell population. This will benefit our fundamental understanding of how animals maximise their health throughout life.Read moreRead less
Marsupial genomics: antimicrobial peptides and endangered species conservation. This project aims to use Australia’s unique biodiversity to tackle the global challenge of antimicrobial resistance. Rapid gene duplication and evolution of antimicrobial peptide genes in marsupials provide protection for joeys that are immunologically naïve in the pouch. By characterising immune genes in 10 marsupial species, this project will yield new antimicrobial peptides that can tackle superbugs. Genomic infor ....Marsupial genomics: antimicrobial peptides and endangered species conservation. This project aims to use Australia’s unique biodiversity to tackle the global challenge of antimicrobial resistance. Rapid gene duplication and evolution of antimicrobial peptide genes in marsupials provide protection for joeys that are immunologically naïve in the pouch. By characterising immune genes in 10 marsupial species, this project will yield new antimicrobial peptides that can tackle superbugs. Genomic information will also be used to provide significant benefits, such as improving the long term conservation of our endangered native species in a more appropriate and cost-effective way.Read moreRead less
Will genetic rescue save the Tasmanian devil? This project aims to measure the long-term genetic impacts of the Save the Tasmanian Devil Program’s ‘Wild Devil Recovery’ initiative. The project will determine whether supplementing small populations with individuals that are genetically diverse reduces inbreeding depression. The project will also monitor the impact of supplementation on the evolutionary trajectory of Devil Facial Tumour Disease. The project will train a cohort of conservation scie ....Will genetic rescue save the Tasmanian devil? This project aims to measure the long-term genetic impacts of the Save the Tasmanian Devil Program’s ‘Wild Devil Recovery’ initiative. The project will determine whether supplementing small populations with individuals that are genetically diverse reduces inbreeding depression. The project will also monitor the impact of supplementation on the evolutionary trajectory of Devil Facial Tumour Disease. The project will train a cohort of conservation scientists to translate genetic data into management actions. The outputs will directly inform the management actions of the Tasmanian Department of Primary Industries Parks, Water and the Environment and will help shape other species recovery programs.Read moreRead less
Can parasites cause host population divergence? . Parasites have been proposed to be drivers of population divergence, and ultimately speciation, yet the dynamics of this process are not well understood. This project will utilise new genomic techniques, novel hybrid zone analyses, and data on mate choice, to investigate the hypothesis that parasites drive population divergence through an interaction with immune response genes in the sleepy lizard Tiliqua rugosa. This species provides an unpreced ....Can parasites cause host population divergence? . Parasites have been proposed to be drivers of population divergence, and ultimately speciation, yet the dynamics of this process are not well understood. This project will utilise new genomic techniques, novel hybrid zone analyses, and data on mate choice, to investigate the hypothesis that parasites drive population divergence through an interaction with immune response genes in the sleepy lizard Tiliqua rugosa. This species provides an unprecedented system, backed by 37 years of long term host-parasite and behavioural data, and recent genetic analyses. This project intends to produce significant data to allow an examination of the early stages of host-parasite evolution in action, providing novel insights into the speciation process. Read moreRead less
How do stem cells get specified during embryonic muscle development? This project aims to investigate the mechanisms by which muscle stem cells first form in the embryo. This project expects to generate new knowledge on the mechanism that patterns cell types in the embryonic myotome. Expected outcomes of this project include uncovering the developmental mechanisms of cell type specification in the myotome with specific reference to the generation of stem cells. This should provide significant be ....How do stem cells get specified during embryonic muscle development? This project aims to investigate the mechanisms by which muscle stem cells first form in the embryo. This project expects to generate new knowledge on the mechanism that patterns cell types in the embryonic myotome. Expected outcomes of this project include uncovering the developmental mechanisms of cell type specification in the myotome with specific reference to the generation of stem cells. This should provide significant benefits as it will inform how long lived tissue resident stem cells can be made in the first instance, knowledge that is critical for making stem cells on demand outside the animal and manipulating stem cells in living tissue.Read moreRead less
The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehe ....The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehensively define where in the embryo it is required and investigate what cofactors it interacts with to perform its function. Using genetic zebrafish and mouse models as well as cell culture models we will investigate the fundamental biology of this gene.Read moreRead less
Characterising a new regulator of the Hedgehog pathway . The Hedgehog pathway is crucial for embryonic development, and disruption causes multi-organ morphogenesis defects. The CI team has uncovered a new gene required for Hedgehog signalling in mouse, zebrafish, and Drosophila. Preliminary data hints at mechanism for this novel gene and shows it may in fact be a member of a new superfamily. The project will examine gene function and identify interacting protein partners, using the zebrafish, Dr ....Characterising a new regulator of the Hedgehog pathway . The Hedgehog pathway is crucial for embryonic development, and disruption causes multi-organ morphogenesis defects. The CI team has uncovered a new gene required for Hedgehog signalling in mouse, zebrafish, and Drosophila. Preliminary data hints at mechanism for this novel gene and shows it may in fact be a member of a new superfamily. The project will examine gene function and identify interacting protein partners, using the zebrafish, Drosophila, and cell-based models. Findings will provide basic knowledge about this mysterious gene and uncover how it modulates an essential pathway in embryonic development. This research is expected to impact knowledge generation, health, and well-being.Read moreRead less
Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signa ....Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signalling pathways involved in this novel phenomenon. This should provide significant benefits to our fundamental understanding of biological processes that protect human genomes and provide a valuable dataset for research on telomere biology, DNA repair, and genome stability.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
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