Tuning mesenchymal stem cell lifespan, performance, and differentiation. This project aims to fully characterise a unique molecular process that strongly modulates mesenchymal stem cell lifespan and behaviour. This work is significant, as it is expected to reveal new concepts underpinning the mechanistic actions of classical structural proteins. It will also shape a more nuanced understanding of the context-dependent mechanical and biochemical signals that regulate stem cell fate and function. E ....Tuning mesenchymal stem cell lifespan, performance, and differentiation. This project aims to fully characterise a unique molecular process that strongly modulates mesenchymal stem cell lifespan and behaviour. This work is significant, as it is expected to reveal new concepts underpinning the mechanistic actions of classical structural proteins. It will also shape a more nuanced understanding of the context-dependent mechanical and biochemical signals that regulate stem cell fate and function. Expected outcomes include new knowledge surrounding native extracellular matrix and stem cell biology, and the development of strategies to define and tailor stem cell properties. This work is anticipated to drive new technologies that can efficiently and robustly manipulate stem cells for diverse functional applications.Read moreRead less
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
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
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
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
Magnetically controlled drug release from tissue scaffolds for the treatment of acute burns. Severe skin burns are frequently associated with functionally disabling scarring and the risk of death. New magnetically activated wound seals for the treatment of acute burns will be developed that reduce the need for frequent painful dressing changes and hence facilitate rapid healing with a significantly reduced chance of scarring.
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
Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interaction ....Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interactions and be used as lead compounds for treatments for disease.Read moreRead less
Investigating the activator function of the Bim protein. Apoptosis is a research area where Australia has had long standing success. The first observations of this important process were made by Prof John Kerr in the 60's and 70's. A molecular renaissance developed in the late 80's and has led to the current explosion in this area of research. Many of these recent studies have been conducted at the Walter and Eliza Hall Institute. Our scientific endeavour is aimed at broadening the understanding ....Investigating the activator function of the Bim protein. Apoptosis is a research area where Australia has had long standing success. The first observations of this important process were made by Prof John Kerr in the 60's and 70's. A molecular renaissance developed in the late 80's and has led to the current explosion in this area of research. Many of these recent studies have been conducted at the Walter and Eliza Hall Institute. Our scientific endeavour is aimed at broadening the understanding of the mechanisms of cell death using genetically modified mouse models. Insights gained through this project will have far reaching implications for the design of new drugs to combat cancer and degenerative diseases.Read moreRead less