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.
Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine ....Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine the importance of a family of intracellular signalling enzymes, the Class II phosphoinositide 3-kinases, in platelet function. These studies will define the contribution of these enzymes to platelet production and function and will establish whether their inhibition is an attractive strategy for the prevention of arterial thrombosis.Read moreRead less
Studying precancerous stem cells that cause T cell leukaemia. Recent research has identified abnormal stem cells that are the cause of T cell leukaemia. They are also resistant to therapeutics suggesting that they could be a cause of relapse. The aim of this project is to determine the abnormal pathways that cause these cells to become immortal and to determine new therapeutic strategies to eliminate them.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100043
Funder
Australian Research Council
Funding Amount
$330,000.00
Summary
Development of an ultra-high speed spinning disk confocal micro-particle image velocimetry (PIV) platform for the investigation of cardiovascular disease . This facility will establish a microscope system specifically designed to investigate the function of blood cells in the context of cardiovascular diseases such as heart attack and stroke.
Ex vivo production of neutrophils. Relentless infections frequently occur in patients receiving intensive chemotherapy treatment. Chemotherapy is toxic to the bone marrow where blood cells are produced. A low white blood cell count and in particular a low neutrophil count is linked with infection in these patients. Unlike red cells and platelets, neutrophils are difficult to collect from blood donors and hence are not routinely available. In this project, we will develop a practical, cost effic ....Ex vivo production of neutrophils. Relentless infections frequently occur in patients receiving intensive chemotherapy treatment. Chemotherapy is toxic to the bone marrow where blood cells are produced. A low white blood cell count and in particular a low neutrophil count is linked with infection in these patients. Unlike red cells and platelets, neutrophils are difficult to collect from blood donors and hence are not routinely available. In this project, we will develop a practical, cost efficient process for the production of neutrophils from cord blood. Transfusion of these neutrophils should reduce the chance of patients suffering serious infection, allow them to recover faster from their chemotherapy, and reduce the need for admission to intensive care.Read moreRead less
EX VIVO PRODUCTION OF MATURE RED BLOOD CELLS FOR TRANSFUSION. This project aims to establish a practical, cost efficient biotechnology platform for the expansion and maturation of blood stem cells to produce blood transfusion products. Red blood cell production will be used as the prototype model. It is envisaged that blood bioreactors will initially supplement and ultimately replace the current blood donor based process, thus overcoming the on-going donor recruitment, retention and safety issue ....EX VIVO PRODUCTION OF MATURE RED BLOOD CELLS FOR TRANSFUSION. This project aims to establish a practical, cost efficient biotechnology platform for the expansion and maturation of blood stem cells to produce blood transfusion products. Red blood cell production will be used as the prototype model. It is envisaged that blood bioreactors will initially supplement and ultimately replace the current blood donor based process, thus overcoming the on-going donor recruitment, retention and safety issues associated with collection of single units of blood. This project is focused on providing solutions to two key technical and economical challenges: (a) achieving full maturation of red blood cells and (b) achieving at least a 100-fold intensification of the expansion and maturation process through perfusion.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
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
Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches ....Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches off inflammation. Essential knowledge into why this receptor pathway fails to switch off inflammation will be determined. Furthermore, the development of targeting strategies to this receptor represents an innovative approach to blocking damaging and chronic airway inflammation.Read moreRead less