The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialis ....The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialised high-end microscopy and genetic methods to examine how the nucleus of migrating zebrafish macrophages deforms, repositions and is restructured during migration in living tissues, and how this influences macrophage locomotion. The goal is to provide fundamental insights into the cell biology of macrophage migration.Read moreRead less
Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new pro ....Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new processes of how normal body hormones and administered steroids may function. This may eventually lead to new and more effective ways to control inflammation that will have significant benefits to mammalian health and improve health care and agriculture outcomes.Read moreRead less
Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.Read moreRead less
Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replicati ....Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replication stress response where changes to the architecture of a cell nucleus, and movement of the genomic material inside, promotes repair of genomic damage that occurs during replication. The result of this project will be an understanding of fundamental biological processes that protect human genomes.Read moreRead less
How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent si ....How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent signaling. Expected outcomes include novel insights into environmental control of cell proliferation and forging cross institutional collaborations. This knowledge benefits basic and applied biology and is relevant to industries/projects utilizing living cells as nutrient supports cell survival and proliferation.Read moreRead less
Navigating flux control through a branched metabolic pathway. This project aims to uncover control points and programmes in the mevalonate pathway, an important cellular metabolic pathway that produces cholesterol and isoprenoids. Knowledge of its regulation is largely restricted to just one enzyme (HMGCR). This project will determine how regulation of the later sterol-producing segment affects the early isoprenoid-segment of the mevalonate pathway; investigate how the two alternate routes to ch ....Navigating flux control through a branched metabolic pathway. This project aims to uncover control points and programmes in the mevalonate pathway, an important cellular metabolic pathway that produces cholesterol and isoprenoids. Knowledge of its regulation is largely restricted to just one enzyme (HMGCR). This project will determine how regulation of the later sterol-producing segment affects the early isoprenoid-segment of the mevalonate pathway; investigate how the two alternate routes to cholesterol synthesis operate and are regulated; and explore a co-ordinated and possibly co-operative transcriptional program. This project is expected to provide valuable knowledge of how cells control these critical lipids, which will ultimately inform better ways to treat diseases of cholesterol excess and defects in this pathway.Read moreRead less
Molecular mechanisms determining the lipid composition of synapses. Synapses between neurons play a key role in all functions of the nervous system including learning and memory. They are mostly composed of the unique combination of proteins and lipids, which function together to enable neurotransmission. While the molecular mechanisms determining the protein composition of synapses are well characterised, the mechanisms defining the lipid composition of synapses remain unknown. The project will ....Molecular mechanisms determining the lipid composition of synapses. Synapses between neurons play a key role in all functions of the nervous system including learning and memory. They are mostly composed of the unique combination of proteins and lipids, which function together to enable neurotransmission. While the molecular mechanisms determining the protein composition of synapses are well characterised, the mechanisms defining the lipid composition of synapses remain unknown. The project will use advanced techniques of neuroscience and lipid research to determine the mechanisms of lipid transport and retention at synapses. The project is expected to generate new knowledge about the fundamental mechanisms of brain function, which will be useful for developing new therapeutics enhancing the brain power.Read moreRead less
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered i ....Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered inside the cell as it tries to recover. It will give a much greater understanding of mitochondrial damage at the microscopic level, and has the potential to unlock new avenues of investigation into the causes of inflammatory and immune disorders.Read moreRead less