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
Understanding glycopolymer interactions with the extracellular matrix. This project aims to advance knowledge of the biochemical and biophysical structure of the endothelial glycocalyx, a dynamic cell surface extracellular matrix rich in proteoglycans and glycosaminoglycans. It will be the first to explore how charged glycopolymers interact with this dynamic interface with the goal to develop a model of the glycocalyx lifecycle. This project is expected to enable the transfer of skills, knowledg ....Understanding glycopolymer interactions with the extracellular matrix. This project aims to advance knowledge of the biochemical and biophysical structure of the endothelial glycocalyx, a dynamic cell surface extracellular matrix rich in proteoglycans and glycosaminoglycans. It will be the first to explore how charged glycopolymers interact with this dynamic interface with the goal to develop a model of the glycocalyx lifecycle. This project is expected to enable the transfer of skills, knowledge and ideas as well as advanced research and industrial training for young scientists. Knowledge derived from this project is expected to enable future innovation in molecules with tailored interactions with the glycocalyx with significant benefits for researchers, manufacturers and end users. Read moreRead less
Engineering nanomaterial interactions with the cell surface. This Fellowship aims to advance understanding of the endothelial cell surface, a key tissue barrier, and its interactions with nanomaterials. Enabled by cross-disciplinary collaboration, it expects to develop knowledge in matrix biology of the cell surface and materials as well as new methods to analyse their interactions. This is expected to unravel causal relationships between nanomaterial features and interactions at the cell surfac ....Engineering nanomaterial interactions with the cell surface. This Fellowship aims to advance understanding of the endothelial cell surface, a key tissue barrier, and its interactions with nanomaterials. Enabled by cross-disciplinary collaboration, it expects to develop knowledge in matrix biology of the cell surface and materials as well as new methods to analyse their interactions. This is expected to unravel causal relationships between nanomaterial features and interactions at the cell surface which will be integrated to engineer optimised materials. This will address the current and critical challenges of nanomaterial technologies in the efficient and targeted interactions with cells with long-term benefits for the consumer, biotechnology and healthcare sectors.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
Sugar transporters in coral symbiosis and origin of parasitism. We aim to identify how symbiotic algae feed sugar to their coral hosts. Corals need this algal sugar to exist, but no one knows how it is transferred, so understanding this crucial mechanism is hugely significant. The first benefit of this research will be a fundamental understanding about how two organisms (algae and coral) cooperate to build habitats like the Great Barrier Reef. We also aim to explore whether coral/algal coopera ....Sugar transporters in coral symbiosis and origin of parasitism. We aim to identify how symbiotic algae feed sugar to their coral hosts. Corals need this algal sugar to exist, but no one knows how it is transferred, so understanding this crucial mechanism is hugely significant. The first benefit of this research will be a fundamental understanding about how two organisms (algae and coral) cooperate to build habitats like the Great Barrier Reef. We also aim to explore whether coral/algal cooperation paved the way for the origin of parasitism. The second key outcome will be to identify the precise molecular mechanism that allowed parasitism to arise. This will benefit us through understanding the origins of important diseases such as human malaria and related infections of livestock and wildlife.
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Chemical staples and chemical probes to dissect dynamins cellular roles. Modulation of protein structure drives cellular function. Dynamin GTPase forms at least two macromolecular structures with different cellular functions. The drivers behind these different structures is unknown. In this project we will leverage our discoveries, and planned enhancements, of chemical biology probes that will modulate dynamin activity by inhibiting at three distinct sites, and one site that stimulates dynamin a ....Chemical staples and chemical probes to dissect dynamins cellular roles. Modulation of protein structure drives cellular function. Dynamin GTPase forms at least two macromolecular structures with different cellular functions. The drivers behind these different structures is unknown. In this project we will leverage our discoveries, and planned enhancements, of chemical biology probes that will modulate dynamin activity by inhibiting at three distinct sites, and one site that stimulates dynamin activity. It is known that Dynamin helices and rings are believed responsible for at least three in cell biological functions: in hormone, neutral and receptor internalisation; cellular mitosis and in actin dynamics. Prior to this work we have lacked the tools to understand the role of shape modulation of protein function.Read moreRead less
Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacte ....Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacteria, and a richer understanding of how these proteins have evolved over the last 4 billion years. This promises significant benefits in the form of new ways to address the challenge posed by antimicrobial resistance to antibiotics, which is a serious threat to the continued effectiveness of current antibiotics.Read moreRead less
Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. ....Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. It will also develop new 3D models to simulate conditions in the human body for more rapid testing of electrodes. The new knowledge generated will improve the accuracy of predictions of platinum dissolution, develop new approaches for minimising dissolution, and contribute to reducing need for animal experimentation.Read moreRead less