How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pat ....How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pathways required for enucleation. The project will provide a molecular and cellular road map of enucleation that may be utilised to enhance the bulk therapeutic in vitro production of red blood cells for veterinary and human purposes.Read moreRead less
Synthetic leukocytes: bio-inspired DNA nanorobots powered by flow. Inspired by the way white blood cells roll along blood vessel walls, our goal is to build DNA nanorobots that roll along surfaces in flow. We take a synthetic biology approach to using biomolecules, such as DNA and proteins, to build functional particles and surfaces. To achieve this, we will combine our teams’ technological advances in DNA nanotechnology, plasma-activation for biomolecule immobilisation, and microfluidic devices ....Synthetic leukocytes: bio-inspired DNA nanorobots powered by flow. Inspired by the way white blood cells roll along blood vessel walls, our goal is to build DNA nanorobots that roll along surfaces in flow. We take a synthetic biology approach to using biomolecules, such as DNA and proteins, to build functional particles and surfaces. To achieve this, we will combine our teams’ technological advances in DNA nanotechnology, plasma-activation for biomolecule immobilisation, and microfluidic devices. This project will contribute new methods for synthetic particle motion in flow and provide new insights into biomolecule interactions and motion. Ultimately, this will allow us to harness rolling for the delivery of synthetic nanorobots for detection and remediation in flow systems, such as the body.Read moreRead less
Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and de ....Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and degenerative diseases. Also, a strong bridge will be built upon the previous collaborations of the research teams in Brisbane and Pennsylvania, which will facilitate advanced teaching and training of Australian PhD and post-doctoral scientists.Read moreRead less
Pathogen sensing in systemic inflammatory disease. The initiation, amplification and quenching of an immune response is a carefully orchestrated process that eliminates invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that restrict immune responses to prevent inflammatory diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. This work will also explore the role of a potassium channel that protects the host from or ....Pathogen sensing in systemic inflammatory disease. The initiation, amplification and quenching of an immune response is a carefully orchestrated process that eliminates invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that restrict immune responses to prevent inflammatory diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. This work will also explore the role of a potassium channel that protects the host from organ failure during an infection, by coupling the energy requirements of mounting an immune response, and organ function. This may have important implications for the management of sepsis, a systemic immune response associated with infection and the leading cause of death in critically ill patients.Read moreRead less
Socs proteins in development and disease. Socs proteins are a component of a pathway that is central to a range of developmental processes, including embryonic development. In addition, there is evidence that these proteins are perturbed in several disorders. This Project will enhance our understanding of the Socs proteins and their role in disease, and ultimately provide an opportunity to identify new therapeutic strategies.