Neurons and neurotransmitters that control the apnoeic response to irritation of the larynx. Normal function of the larynx enables breathing, cough, singing, speech and many other normal functions. This project will reveal how nerves in the brain coordinate to achieve these many functions; in particular the way that breathing stops if fluid or smoke enters the larynx.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Treating tuberculosis: targeted delivery of multidrug nano-suspensions. Tuberculosis (TB) is a lung disease of worldwide prevalence. Treatment times are long and mortality is high in children and the elderly. Current treatments are ineffective and drug resistant TB is a real pandemic threat. The project will develop a cost-effective nano-particle system that can be incorporated into conventional nebulisers for use worldwide.
Development of microbial bioproducts for the suppression of inflammation. Asthma and inflammatory diseases are serious health problems that result from excessive inflammation. Exposure to bacteria may reduce inflammation. This project will identify the bacterial components that reduce inflammation and develop them into new anti-inflammatory therapies for asthma.
Novel kinases: How do they regulate epithelial ion transport, and what is their role in epithelial function? The project will produce the knowledge of fundamental physiology that will lead to novel approaches for treating respiratory and gastrointestinal infections and cystic fibrosis, as well as for the accumulation of fluid in the lungs and abdomen that accompany many advanced malignancies. It thus has the potential to have a significant economic and social impact in Australia and internation ....Novel kinases: How do they regulate epithelial ion transport, and what is their role in epithelial function? The project will produce the knowledge of fundamental physiology that will lead to novel approaches for treating respiratory and gastrointestinal infections and cystic fibrosis, as well as for the accumulation of fluid in the lungs and abdomen that accompany many advanced malignancies. It thus has the potential to have a significant economic and social impact in Australia and internationally. Furthermore, it will provide advanced training in research methods to Australian scientists, equipping them to undertake challenging and interesting positions in the medical and life sciences and beyond.Read moreRead less
Matched experimental observation and finite-element simulation of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this couple ....Matched experimental observation and finite-element simulation of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this coupled system (the fluid flow interacts with the tube shape), we seek to demonstrate for the first time that a given theory/computer model encompasses the physics controlling a given observed oscillation. The solution will find application in other flexible-structure design problems in engineering, and also potentially in medicine.Read moreRead less
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less
Central command neurons integrating cardiorespiratory drive in exercise. The ability to perform exercise is fundamental to human health and welfare. This ability depends upon the co-ordination by the brain of respiratory and cardiovascular function, such that the delivery of oxygen to exercising muscles is maximised. This project will test the idea that there is a specific group of neurons in the brain that drive both the respiratory and cardiovascular changes that occur during exercise, and w ....Central command neurons integrating cardiorespiratory drive in exercise. The ability to perform exercise is fundamental to human health and welfare. This ability depends upon the co-ordination by the brain of respiratory and cardiovascular function, such that the delivery of oxygen to exercising muscles is maximised. This project will test the idea that there is a specific group of neurons in the brain that drive both the respiratory and cardiovascular changes that occur during exercise, and will determine the location and functions of such neurons. Such new knowledge will help us understand how the brain optimises the ability of the body to perform exercise. This is of fundamental importance in sports science, a field in which Australia excels.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.