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
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 potency and role of individual stem cells in the skin using Rainbow technology. To renew itself, the skin and its components rely on the activity of stem cells. This project will define more precisely the role of each individual stem cell by labelling them with a unique colour and following its fate. This project has the potential to change our current view on how the skin maintains and repairs itself.
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.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
Chemical principles underpinning a spermostatic-microbiostatic agent capable of preventing pregnancy and the spread of sexually transmitted disease. This project explores the development of a method for simultaneously controlling fertility while preventing the spread of sexually transmitted diseases. A novel aspect of the approach, that will dramatically influence product development, is that the active principles will only be generated on contact with seminal plasma.
Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and w ....Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and whether neurogenesis may be induced by inflammation in the adult. Using transcriptomics we will also determine how the neurogenic environment changes with age/inflammation. This project is an important step in proving that the brain's potential to generate new neurons extends beyond infancy.Read moreRead less
The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciph ....The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciphering basic biological mechanisms, patenting new data, developing treatment strategies for un-curable and fatal disorders, and expanding links to Australian biotech and international pharmaceutical companies.Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient c ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient compliance. We will conduct critical chemical and biological experiments with a new series of potentially orally active iron chelators identified in our lab. The results from this project will be vital for the development of these compounds as pharmaceuticals.Read moreRead less