Modulation of protein folding pathways: a new platform technology for molecular medicine. Misfolding of proteins is becoming recognised as a major cause of inherited disease. We propose to develop a chemical agent that will optimise the folding of alpha1-antitrypsin (AAT), misfolding of which gives rise to inheritable liver and lung disease. This agent will have potential application as a therapy for sufferers of AAT-misfolding disease and for improving the yield of AAT purified from human plasm ....Modulation of protein folding pathways: a new platform technology for molecular medicine. Misfolding of proteins is becoming recognised as a major cause of inherited disease. We propose to develop a chemical agent that will optimise the folding of alpha1-antitrypsin (AAT), misfolding of which gives rise to inheritable liver and lung disease. This agent will have potential application as a therapy for sufferers of AAT-misfolding disease and for improving the yield of AAT purified from human plasma, which is the current agent used to treat patients with AAT-misfolding disease.Read moreRead less
The Production of Respiratory Cell Lineages from Human Embryonic Stem Cells: Towards a Cell Replacement Therapy for the Treatment of Respiratory Specific Deficits. Embryonic stem (ES) cells are a primitive embryonic cell type that can be maintained and grown in vitro. Mouse ES cells can be instructed to develop into a wide range of specific adult cell types. Research into human ES cells has more recently commenced and has already resulted in the controlled production of specific nerve cells by o ....The Production of Respiratory Cell Lineages from Human Embryonic Stem Cells: Towards a Cell Replacement Therapy for the Treatment of Respiratory Specific Deficits. Embryonic stem (ES) cells are a primitive embryonic cell type that can be maintained and grown in vitro. Mouse ES cells can be instructed to develop into a wide range of specific adult cell types. Research into human ES cells has more recently commenced and has already resulted in the controlled production of specific nerve cells by our group. The following project aims to create respiratory lineages from both mouse and human ES cells. Such an undertaking thus aims to provide a basis for the treatment of respiratory specific diseases such as cystic fibrosis and emphysema.Read moreRead less
Cellular genomic approach to the pathogenesis of multiple sclerosis. This project compares the levels of gene usage in two important immune cell types between patients with multiple sclerosis and people who do not have the disease. It aims to identify the molecular basis for the disease, in order to identify new diagnostic, preventative and treatment options.
Increasing the utility of tetanus toxins by protein engineering. There are a variety of common diseases that are the result of muscular defects. Some of these may be able to be treated with an agent that increases muscle tone, thereby giving benefit to the patient in the alleviation of symptoms. This project aims to use some of the most potent substances known, bacterial toxins, and engineer them to be valuable agents for treatment of certain muscular disorders.
The Fluid-Particle Mechanics of a Synthetic Jet-based Dry Powder Inhaler. This project aims to untangle the fundamental principles that govern the fluid mechanics and particulate interactions in a novel concept chip-based micro-zero-net-mass-flux (micro-ZNMF) jet-assisted dry powder inhaler (DPI). Respiratory diseases affect 6.2 million Australians. The treatment of these diseases is hampered by the poor efficiency of current delivery systems, with conventional DPI devices exhibiting sub-optimum ....The Fluid-Particle Mechanics of a Synthetic Jet-based Dry Powder Inhaler. This project aims to untangle the fundamental principles that govern the fluid mechanics and particulate interactions in a novel concept chip-based micro-zero-net-mass-flux (micro-ZNMF) jet-assisted dry powder inhaler (DPI). Respiratory diseases affect 6.2 million Australians. The treatment of these diseases is hampered by the poor efficiency of current delivery systems, with conventional DPI devices exhibiting sub-optimum performance, delivering typically less than 20% of the loaded dose to the target site, the lungs. The new fundamental knowledge resulting from this research will enable the engineering of a high-efficiency groundbreaking DPI, with the potential to be fully adaptive user-specific benefiting millions of Australians. Read moreRead less
Improving respiratory drug delivery through targeted nozzle design. The project aims to develop designs for inhaler components which significantly reduce the existing variability in the sprays they produce, as well as an enhanced capacity to predict inhaler performance through development of new empirical models. This project will combine recently developed synchrotron x-ray measurement techniques with traditional visible light diagnostics to develop a greater understanding of the link between t ....Improving respiratory drug delivery through targeted nozzle design. The project aims to develop designs for inhaler components which significantly reduce the existing variability in the sprays they produce, as well as an enhanced capacity to predict inhaler performance through development of new empirical models. This project will combine recently developed synchrotron x-ray measurement techniques with traditional visible light diagnostics to develop a greater understanding of the link between the geometry of pressurised, metered-dose inhaler components and the drug particles these devices produce. The long term benefit from this research will be improved delivery efficiency and shorter product development times, leading to reduced dose-rate costs. This understanding will enable the development of the next generation of treatment devices with enhanced efficiency in delivery of the drugs used to treat these diseases and reduced costs per dose.Read moreRead less
Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to ....Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to discover the specificity of PAT-SM6 for proteins and protein complexes and how these interactions lead to tumour cell death. This work will enhance the effectiveness of human antibody therapies and help in the development of this fast growing area within the biotechnology industry in Australia.Read moreRead less
Bilateral Cochlear Implants for Children: Does a Second Implant Improve Language, Psychosocial and Other Outcomes? Severe-profound congenital hearing loss engenders significant costs to society. In 2005, specialised education cost -- on average $25,000 per child, loss of productivity cost -- $6.7 billion, and social security benefits were paid to approximately 129,000 individuals who were unemployed due to hearing loss. If bilateral cochlear implantation results in improved language, social dev ....Bilateral Cochlear Implants for Children: Does a Second Implant Improve Language, Psychosocial and Other Outcomes? Severe-profound congenital hearing loss engenders significant costs to society. In 2005, specialised education cost -- on average $25,000 per child, loss of productivity cost -- $6.7 billion, and social security benefits were paid to approximately 129,000 individuals who were unemployed due to hearing loss. If bilateral cochlear implantation results in improved language, social development, and academic outcomes, the community benefits arising will be greatly improved quality of life for these individuals and significant savings to society. In partnership with Cochlear Ltd, this study will provide some of the first data worldwide comparing the effects of an additional implant on language, social and educational outcomes.Read moreRead less
Chemical Synthesis and Biological Evaluation of Analogues of Platencin, a New-generation Antibiotic. The just discovered natural product platencin displays potent and broad spectrum anti-bacterial activity. It may represent the precursor of a new class of drugs to replace current anti-infective agents which are becoming alarmingly less effective as bacterial resistance increases dramatically. For this reason, platencin has been described as a once in a generation discovery. This study will explo ....Chemical Synthesis and Biological Evaluation of Analogues of Platencin, a New-generation Antibiotic. The just discovered natural product platencin displays potent and broad spectrum anti-bacterial activity. It may represent the precursor of a new class of drugs to replace current anti-infective agents which are becoming alarmingly less effective as bacterial resistance increases dramatically. For this reason, platencin has been described as a once in a generation discovery. This study will exploit two sophisticated new synthetic techniques for the purposes of making analogues of platencin that will be screened by the industry partner, Biota, for anti-bacterial properties. New drug candidates capable of treating especially dangerous infections such as methicillin resistant staphyllococcus aureus (MRSA) should thus emerge.Read moreRead less
Optimising bubble continuous positive airway pressure (CPAP) for preterm infants. Synchrotron imaging will be used to see how the lungs of newborns are aerated and move when they are supported by continuous positive airway pressure (CPAP) breathing support. This project will provide fundamental biological information that will contribute to refinement of devices to support breathing in babies.