Dynamic Microcages for Cells: Advanced Tools to Interrogate Cell Mechanics. This project aims to develop a suite of movable micro/nanostructures with integrated mechanical and biological sensors, which will be interfaced with cells to investigate how those cells respond to their surrounding physical environment. Expected outcomes are new technologies in micro/nanofabrication, sensing, and advanced imaging, and deep understanding of the biological processes that control tissue formation and repai ....Dynamic Microcages for Cells: Advanced Tools to Interrogate Cell Mechanics. This project aims to develop a suite of movable micro/nanostructures with integrated mechanical and biological sensors, which will be interfaced with cells to investigate how those cells respond to their surrounding physical environment. Expected outcomes are new technologies in micro/nanofabrication, sensing, and advanced imaging, and deep understanding of the biological processes that control tissue formation and repair. These outcomes would impact how 3D microsystems are developed and applied, informing the design of advanced in-vitro cell culture systems. Significant benefits are expected in 3D nano-microengineering, and in generating new knowledge underpinning future advances in stem cell and tissue engineering technologies.Read moreRead less
Photoreversible hydrogels to study stem cell memory and fate. This project will develop materials whose stiffness can be reversibly increased and decreased by the simple application of light, and use these to build knowledge of how stem cell fate is regulated. The influence of mechanical cues on the structure and organisation of the nucleus will be determined. Expected outcomes are new synthetic and light-reversible culture materials, and fundamental insights into how forces change the nucleus t ....Photoreversible hydrogels to study stem cell memory and fate. This project will develop materials whose stiffness can be reversibly increased and decreased by the simple application of light, and use these to build knowledge of how stem cell fate is regulated. The influence of mechanical cues on the structure and organisation of the nucleus will be determined. Expected outcomes are new synthetic and light-reversible culture materials, and fundamental insights into how forces change the nucleus to alter stem cell aging and fate. The findings will provide critical information required for the future development of assays to measure cell potency and instructive biomaterials to drive stem cell expansion and tissue-regeneration and will have impact by underpinning future advances in stem cell technologies.Read moreRead less
Dual Stimulation Approach to Stem Cell Based Tissue Engineering. This Project aims to determine how human stem cells differentiate into different cell types in response to electrical and mechanical stimulation on a conductive biomaterial platform, and to use this knowledge to develop a custom built bioreactor. It expects to generate new insight into the mechanisms that control stem cell fate using innovative single cell measurements, and will deliver a bioreactor capable of using these mechanism ....Dual Stimulation Approach to Stem Cell Based Tissue Engineering. This Project aims to determine how human stem cells differentiate into different cell types in response to electrical and mechanical stimulation on a conductive biomaterial platform, and to use this knowledge to develop a custom built bioreactor. It expects to generate new insight into the mechanisms that control stem cell fate using innovative single cell measurements, and will deliver a bioreactor capable of using these mechanisms for large scale stem cell differentiation. The expected outcomes are a significant advancement in knowledge in the field of tissue engineering and more efficient methodology for patient-derived stem cell therapy. This will provide new pathways to improving stem cell therapy for tissue engineering applications.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 capacity for exceptional brain repair in a novel rodent species. This project aims to provide a new and much-needed living tool for studying brain injury and repair. The project expects to generate new evidence of effective brain repair in a mammalian species, the spiny mouse. In particular, it will provide important knowledge of the cellular responses that coordinate to allow mammalian brain repair, revealing targets for future understanding and treatment. Expected outcomes include an in-de ....The capacity for exceptional brain repair in a novel rodent species. This project aims to provide a new and much-needed living tool for studying brain injury and repair. The project expects to generate new evidence of effective brain repair in a mammalian species, the spiny mouse. In particular, it will provide important knowledge of the cellular responses that coordinate to allow mammalian brain repair, revealing targets for future understanding and treatment. Expected outcomes include an in-depth characterisation of how neurons and non-neuronal cells (glia) contribute to brain repair, and the identification of new pathways or targets for mammalian brain repair. In the long-term this should provide significant benefits for future research focused on improving the lives of people affected by brain injury. Read moreRead less
An anti-senescence nanoplatform and its underlying mechanism. The project will bring together complementary expertise and skills by combining biomaterials, cell and molecular biology, and engineering, to develop a novel nano-biomaterial platform for anti-senescence and gain an in-depth understanding of its underlying mechanisms. The underlying mechanisms of senescence remain elusive and bone substitutes with anti-senescence property have not been explored and becoming a growing field of interest ....An anti-senescence nanoplatform and its underlying mechanism. The project will bring together complementary expertise and skills by combining biomaterials, cell and molecular biology, and engineering, to develop a novel nano-biomaterial platform for anti-senescence and gain an in-depth understanding of its underlying mechanisms. The underlying mechanisms of senescence remain elusive and bone substitutes with anti-senescence property have not been explored and becoming a growing field of interest in bone regeneration. The project will develop a well-defined and efficient nanomaterial platform with optimal combination of nano-surface features and chemistry for cell rejuvenation, and it will give unprecedented depth of interdisciplinary understanding of senescence rejuvenation mechanisms.Read moreRead less
How do transcription factors control cell fate transitions? The aim of this project is to determine how transcription factors control cellular identity, which is relevant to many biological processes including embryogenesis, cellular reprogramming and differentiation. Innovative genomic tools will be combined with various in vitro cellular conversion systems to generate fundamental mechanistic insight into how transcription factors mediate these identity changes. The knowledge gained from this w ....How do transcription factors control cell fate transitions? The aim of this project is to determine how transcription factors control cellular identity, which is relevant to many biological processes including embryogenesis, cellular reprogramming and differentiation. Innovative genomic tools will be combined with various in vitro cellular conversion systems to generate fundamental mechanistic insight into how transcription factors mediate these identity changes. The knowledge gained from this work will allow us to answer standing fundamental questions in regards to cell fate control and the biochemistry of transcription factors, which in turn will aid in the development of novel gene regulation technologies applicable to a myriad of fields and industries.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
Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined wit ....Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined with innovative analysis, we propose to define and validate each cell state at the molecular level.
This new knowledge would greatly enhance our ability to control the transition between cell states leading to a more widespread use of endothelial cells in bioengineering of tissues globally for many applications.
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The role of protein glycosylation in erythropoiesis . This project aims to understand how the sugar code of key-signalling proteins influences the development of red blood cells. This project expects to generate new fundamental knowledge in the area of stem cell signalling by innovative integration of biological and computational molecular characterisation techniques. The expected outcomes of this project include the development of novel workflows to study key regulators of cell development and ....The role of protein glycosylation in erythropoiesis . This project aims to understand how the sugar code of key-signalling proteins influences the development of red blood cells. This project expects to generate new fundamental knowledge in the area of stem cell signalling by innovative integration of biological and computational molecular characterisation techniques. The expected outcomes of this project include the development of novel workflows to study key regulators of cell development and the generation of new knowledge in stem cell signalling that will find applications in transforming stem cell therapies and associated research for future applications such as the laboratory manufacturing of red blood cells to close the availability gap for transfusion purposes.Read moreRead less