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.
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
Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.
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
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
In-vivo detection of airway injury and disease using phase contrast X-ray velocimetry. Currently diagnosis of lung disease, a major cause of death in humans, is based on clinical symptoms that do not usually manifest until the disease is well advanced. This project will develop a novel imaging technique, X-ray velocimetry, to detect changes in tissue before symptoms arise, potentially leading to strategies for managing lung diseases.
Low dose methods for detecting early lung disease using x-ray phase contrast imaging. This project will develop a highly sensitive, low-dose x-ray imaging technique for the early detection of diseases of the respiratory system. This technology will have the potential to be used as a diagnostic screening tool to reduce the incidence of respiratory related deaths from diseases such as lung cancer and emphysema.
The role of electrostatic charge in airway deposition of aerosols. This project aims to unravel the importance of electrostatic charge in controlling deposition of aerosols in the respiratory tract. The expected outcome is a validated mathematical model for accurately predicting deposition behaviour of charged aerosol particles in human airways. Findings may ultimately be used to underpin novel prevention measures to reduce lung deposition of inhaled hazardous airborne particles to significantly ....The role of electrostatic charge in airway deposition of aerosols. This project aims to unravel the importance of electrostatic charge in controlling deposition of aerosols in the respiratory tract. The expected outcome is a validated mathematical model for accurately predicting deposition behaviour of charged aerosol particles in human airways. Findings may ultimately be used to underpin novel prevention measures to reduce lung deposition of inhaled hazardous airborne particles to significantly reduce health risks and costs. They may also be used to enable the development of new inhalation technologies based on electrostatic charge to improve aerosol drug delivery to the lungs of patients with respiratory diseases.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