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
Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less
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
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to r ....Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to rapidly, at high resolution, elucidate how mechanotransductive cues determine the fate choice of mesenchymal stem cells, and furthermore, how to manipulate them with smart biomaterial design to achieve desired outcomes for tissue engineering. Read moreRead less
Potency and activity of Meso-Endothelial bipotent progenitors in vivo. This project aims to characterise a new stem cell population that can maintain both blood vessels and contribute to a variety of tissues whether fibrous, bone, fat or cartilage. Blood vessels comprise an inner endothelial layer and surrounding mesenchyme, are integral to many organs and constitute a unique system connecting different parts of the body. Despite their importance little is known about how they are maintained and ....Potency and activity of Meso-Endothelial bipotent progenitors in vivo. This project aims to characterise a new stem cell population that can maintain both blood vessels and contribute to a variety of tissues whether fibrous, bone, fat or cartilage. Blood vessels comprise an inner endothelial layer and surrounding mesenchyme, are integral to many organs and constitute a unique system connecting different parts of the body. Despite their importance little is known about how they are maintained and how they contribute to the response to injury. Previous work has described several populations of stem cell capable of self renewal and repletion of the endothelium or the mesenchyme. This project will examine the potency of these different progenitors to give rise to each of these fates in homeostasis but also during sounding and bone formation. This will help define a unique population of stem cells capable of both vascular and mesenchymal repair.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
Discovery Early Career Researcher Award - Grant ID: DE170100398
Funder
Australian Research Council
Funding Amount
$410,507.00
Summary
How T cells modulate stem cells and tissue regeneration. The project aims to determine how T cells modulate tissue repair and regeneration in mammals. Most of the mechanisms modulating the healing of tissues are elusive. This research is expected to reveal unknown mechanisms controlling the processes of tissue repair and regeneration, particularly the nexus between the stem cells involved in the tissue healing process and the immune response .