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
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
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
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.
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
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
Developing the basis for an quality control platform for human pluripotent stem cells and their differentiated derivatives. Biophotonic techniques based on spectroscopy have the potential to provide low-cost, automatable measurements for the quality control of stem and differentiated cells produced for use in industry and regenerative medicine. This project is aimed at acquiring the fundamental scientific knowledge base required to bring this about.
Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate re ....Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate regeneration. Ultimately, this works aims to understand the metabolic requirements for regeneration. Expected outcomes include scholarly publications revealing fundamental principles of regeneration, new resources and pipelines for the research community as well as training for research students.Read moreRead less
Final frontier in computational modelling of movement. This project aims to create the computational models and methods needed to advance current understanding of musculoskeletal function during movement. Humans must maintain their capacity to move in order to maintain quality-of-life. Predictive modelling is potentially the most powerful approach for understanding musculoskeletal function during movement. Current computational methods are too slow and unreliable to deliver predictive simulation ....Final frontier in computational modelling of movement. This project aims to create the computational models and methods needed to advance current understanding of musculoskeletal function during movement. Humans must maintain their capacity to move in order to maintain quality-of-life. Predictive modelling is potentially the most powerful approach for understanding musculoskeletal function during movement. Current computational methods are too slow and unreliable to deliver predictive simulations of movement using realistic models of muscle and joint anatomy. This project expects to create the next generation of methods and algorithms needed to enable predictive modelling of movement. Predictive simulations will provide new insights into how muscles stabilise and control movements of the spine, pelvis and lower limbs during daily activities such as walking.Read moreRead less
Accurate Prediction of Safe Life of Buried Pipelines. Failures of buried pipes are disastrous, causing severe consequences and disruptions. They often reoccur because the fundamental cause-effect relation for pipe failures has not been fully understood and hence the safe life of pipelines cannot be reliably predicted. The aim of this research is to develop a new theory to predict pipe failures, based on a fundamental analysis of pipe behaviour and failure mechanisms and a reliability approach. T ....Accurate Prediction of Safe Life of Buried Pipelines. Failures of buried pipes are disastrous, causing severe consequences and disruptions. They often reoccur because the fundamental cause-effect relation for pipe failures has not been fully understood and hence the safe life of pipelines cannot be reliably predicted. The aim of this research is to develop a new theory to predict pipe failures, based on a fundamental analysis of pipe behaviour and failure mechanisms and a reliability approach. The outcomes will be a suite of models and solutions that will advance knowledge in deterioration science and failure theory. They will provide a sustainable solution to the intelligent management of buried pipelines throughout the world.Read moreRead less