Dissecting the physiology of multipotent mesenchymal stromal cells to develop vaccine candidates for respiratory disease. The project aims to gain an understanding of how a type of adult stem cell inhibits immune responses that cause asthma. The project will produce new stem cell products and facilitate the design of a vaccine for asthma and other respiratory diseases, which would greatly reduce the burden of such conditions.
Discovery Early Career Researcher Award - Grant ID: DE130100986
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
An innovative platform using non-coding ribonucleic acids (RNAs) to control stem cell differentiation outcomes. It is difficult to control the tissue type that stem cells will form when combined with biomaterials, as the outcome is influenced by the 'stiffness' of the surface to which the stem cells attach. This project will determine how non-coding ribonucleic acids (RNAs) control stem cell behaviours and use this information to direct stem cell differentiation outcomes.
Redefining tissue-specific endothelial cells through bioengineered matrices. This project aims to improve our understanding of the biological mechanisms that drive blood vessel formation and function. The endothelial cells that make up each blood vessel are inherently unique across different sites within the human body and this project expects to generate new knowledge regarding their organ specificity. Using advanced bioengineering approaches, this project will map human endothelial cell specif ....Redefining tissue-specific endothelial cells through bioengineered matrices. This project aims to improve our understanding of the biological mechanisms that drive blood vessel formation and function. The endothelial cells that make up each blood vessel are inherently unique across different sites within the human body and this project expects to generate new knowledge regarding their organ specificity. Using advanced bioengineering approaches, this project will map human endothelial cell specificity and develop state-of-the-art modelling technologies to improve knowledge of environmental influence on endothelial cell fate and function. This should provide a new framework to modulate the adaptive capacities of endothelial cells and can potentially enable more predictive and targeted drug efficacy and safety testing.Read moreRead less
A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interac ....A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interactions, which will greatly complement existing meta-omics approaches. The deliverables include a proof-of-concept system validated for gut-liver axis as well as the creation of new knowledge and framework to assimilate design thinking and advanced manufacturing to elevate tissue engineering into physiology engineering. Read moreRead less
The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
Micro/nano smart surfaces to unlock the potential of multipotent stem cells. This project aims to determine the interplay of micro/nanostructures on stem cell mechanotransduction and to control the cellular environment. It is expected that this will expand our knowledge on how to control stem cell fate. Expected outcomes are novel scalable technologies for micro/nanostructures and smart surfaces, controlled stem-cell expansion and differentiation, and the creation of a library of protein express ....Micro/nano smart surfaces to unlock the potential of multipotent stem cells. This project aims to determine the interplay of micro/nanostructures on stem cell mechanotransduction and to control the cellular environment. It is expected that this will expand our knowledge on how to control stem cell fate. Expected outcomes are novel scalable technologies for micro/nanostructures and smart surfaces, controlled stem-cell expansion and differentiation, and the creation of a library of protein expression based on the cell interactions. These outcomes will provide critical information required for the future development of instructive biomaterials to drive stem cell expansion and tissue-regeneration. Those materials should benefit the future development of efficient and cost-effective regenerative medicine solutions.Read moreRead less
Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how th ....Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how the human genome is replicated. This knowledge is expected to generate research publications of high quality and provide economic benefits, such as unlocking new potentially patentable DNA technologies. Read moreRead less
Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolut ....Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolution of live imaging to the single molecule to understand the dynamics of actin assembly with implications for cellular processes that are hijacked in diseases. It also aims to provide a novel assay that may enable testing of the impact of drugs on cellular processes in real time.Read moreRead less
The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes ....The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes to characterise the structure and function of a newly identified copper-dependent form of cell enzyme which could be involved in amplifying ubiquitin-tagged protein breakdown. Copper is essential for life in all domains. Identifying copper as a major regulator in protein clearance is important in understanding this fundamental biological machinery.Read moreRead less
Regulation of 3D Cell Migration by Microtubule-Dependent Processes. The overarching aim of this research is to elucidate the molecular mechanisms that cells use to move in 3D environments: a basic biological function essential to development and homeostasis. During these processes, cells interact with their surroundings where they translate biophysical forces into biochemical signals to adapt their shape to move. This requires distinct signalling, controlled in space and time, to regulate the cr ....Regulation of 3D Cell Migration by Microtubule-Dependent Processes. The overarching aim of this research is to elucidate the molecular mechanisms that cells use to move in 3D environments: a basic biological function essential to development and homeostasis. During these processes, cells interact with their surroundings where they translate biophysical forces into biochemical signals to adapt their shape to move. This requires distinct signalling, controlled in space and time, to regulate the crosstalk between organelles and the cytoskeleton. To date, the role of microtubules remains elusive. Using interdisciplinary approaches combining advanced imaging technology with novel cell biology methods, the project aims to uncover fundamental knowledge about how cells interact with their environment.Read moreRead less