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
A Biologically Responsive and Anatomically Authentic Human Nasal Model. As respiratory conditions caused by pollutants and viruses become more prevalent, human nasal models to study infection/protection mechanisms and nasal drug/vaccine delivery are increasingly important. This project aims to develop a world-first human nasal model to mimic both anatomical and biological aspects of the nasal cavity and predict the distribution and deposition of fine particles and the resultant biological respon ....A Biologically Responsive and Anatomically Authentic Human Nasal Model. As respiratory conditions caused by pollutants and viruses become more prevalent, human nasal models to study infection/protection mechanisms and nasal drug/vaccine delivery are increasingly important. This project aims to develop a world-first human nasal model to mimic both anatomical and biological aspects of the nasal cavity and predict the distribution and deposition of fine particles and the resultant biological response from the nasal mucosa. The aim is to overcome a key fabrication challenge - to 3D print an anatomically accurate nasal construct with a porous wall on which to grow and mature functional nasal tissue that lines a nasal cavity wall. The benefit would be enabling faster development of more targeted drugs and vaccines.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
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
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
Understanding the cellular cues that direct muscle stem cell specification. The project aims are to identify the metabolic factors that regulate muscle stem cell identity and to examine how changes in the local metabolic environment can influence how stem cells respond to biological perturbations. One of the most important and unresolved issues in skeletal muscle biology is understanding the role of muscle stem cells in the regulation of growth and development, adaptation and plasticity. We have ....Understanding the cellular cues that direct muscle stem cell specification. The project aims are to identify the metabolic factors that regulate muscle stem cell identity and to examine how changes in the local metabolic environment can influence how stem cells respond to biological perturbations. One of the most important and unresolved issues in skeletal muscle biology is understanding the role of muscle stem cells in the regulation of growth and development, adaptation and plasticity. We have identified that the local skeletal muscle metabolic milieu may regulate the activity of skeletal muscle stem cells. This project could reveal novel mechanisms by which skeletal muscle stem cells can be regulated. This information is crucial for our fundamental understanding of stem cell biology and its future applications.Read moreRead less
Generating multi-component scaffolding to influence the differentiation of embryonic stem cells. Nervous system diseases are debilitating and will develop in over 50 per cent of people at some time in their life. This project will develop strategies so that stem cells can be utilised to encourage brain repair for the treatment of Parkinson's disease. The technology developed will also be of benefit for the treatment of other nervous system disorders.