THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providi ....THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providing only a modest survival advantage (4-6 months) has annual sales of several billion dollars. microRNA represent a relatively newly discovered form of gene activity regulation. Taking a key leadership role in this area will put Australian science at the forefront of international research initiatives.Read moreRead less
Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework f ....Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework for Australian and international cell biologists. It will generate new knowledge, train young Australian scientists, help build international collaborative networks and engage the public outside the research community.Read moreRead less
The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify sma ....The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify smaller early stage inflammasome complexes, for structural analysis. The outcome will be a clearer understanding of processes of caspase activation and inflammasome formation. This will provide significant benefits, such as improve our understanding of processes of cell death and innate immunity, and train students.Read moreRead less
Magnetic Resonance Imaging in Inhomogeneous Magnetic Fields-Part A: The Development of Imaging Methods Using Even Order Zonal Fields. Part B: Slice Correction Due to Non-linear Gradient Fields. The primary aims of this project are to contribute to the new generation of MRI methodologies through technical innovation, with particular emphasis on NMR imaging under inhomogeneous magnetic fields. The new techniques will be of enormous benefit for superconducting magnet design, reducing material usage ....Magnetic Resonance Imaging in Inhomogeneous Magnetic Fields-Part A: The Development of Imaging Methods Using Even Order Zonal Fields. Part B: Slice Correction Due to Non-linear Gradient Fields. The primary aims of this project are to contribute to the new generation of MRI methodologies through technical innovation, with particular emphasis on NMR imaging under inhomogeneous magnetic fields. The new techniques will be of enormous benefit for superconducting magnet design, reducing material usage, and eliminating the need for the expensive post-production shimming process. The entailed project is extremely challenging, while preliminary calculations presented in this application show some progress towards demonstration of feasibility. The program is an ambitious one with a full R&D program over 3 years, which will provide leadership, and to both foster and focus research interest in Australian engineering and scientific endeavors in the field of Magnetic Resonance technology.Read moreRead less
High Field Magnetic Resonance Engineering. The use of high resolution MRI is increasingly important in the quest for molecular imaging and the development of a range of gene therapies, stem cell research and the trialling of new drugs. This research will add momentum to Australia's health technology research community with positive impact on its international research and development profile. Successful outcomes will improve both the applicability and cost-effectiveness of numerous current and ....High Field Magnetic Resonance Engineering. The use of high resolution MRI is increasingly important in the quest for molecular imaging and the development of a range of gene therapies, stem cell research and the trialling of new drugs. This research will add momentum to Australia's health technology research community with positive impact on its international research and development profile. Successful outcomes will improve both the applicability and cost-effectiveness of numerous current and potential medical and non-medical imaging systems with subsequent potential for improved diagnosis in the biotech and health sectors in Australia and overseas. Successful outcomes will provide economic returns through licensing payments from the generated intellectual property.Read moreRead less
Advanced MRI Engineering. Magnetic Resonance Imaging is rapidly becoming the medical imaging modality of choice for soft tissue injuries. The technology development of MRI, however, is relatively young with only 20 years or so of commercial development. The major aim of this project is to contribute to this and the next generation of MRI scanners through technical innovation. New engineering design methods will be developed and used to generate novel superconducting magnet systems and associated ....Advanced MRI Engineering. Magnetic Resonance Imaging is rapidly becoming the medical imaging modality of choice for soft tissue injuries. The technology development of MRI, however, is relatively young with only 20 years or so of commercial development. The major aim of this project is to contribute to this and the next generation of MRI scanners through technical innovation. New engineering design methods will be developed and used to generate novel superconducting magnet systems and associated equipment. A strong focus of the design work will be to include electromagnetic models of the patient in the equipment design. This will not only ensure improved accuracy and speed of MRI scans, but also better patient safety, comfort and clinician access.Read moreRead less
Solutions for reducing magnetic resonance image degradations and tissue heating at high frequencies. This project will contribute to the development of the high-end Magnetic Resonance Imaging (MRI) systems that can substantially improve the image quality, speed of imaging and patient safety in MRI. The project will develop innovative high radio frequency hardware and control methods for imaging. Successful outcomes of this project will, facilitate higher patient throughput in hospitals, provisi ....Solutions for reducing magnetic resonance image degradations and tissue heating at high frequencies. This project will contribute to the development of the high-end Magnetic Resonance Imaging (MRI) systems that can substantially improve the image quality, speed of imaging and patient safety in MRI. The project will develop innovative high radio frequency hardware and control methods for imaging. Successful outcomes of this project will, facilitate higher patient throughput in hospitals, provision of more powerful clinical imaging tools to aid early diagnosis and various research modalities ranging from molecular to real-time imaging during interventional procedures.Read moreRead less
Molecular characterization of the role of menin in embryonic development. Menin is a protein that is necessary to prevent development of tumours. Deletion of menin in mice causes embryonic death. We think this is because menin is necessary in the placenta. This project will examine the role of menin in the fetus and the placenta, and provide information about how normal pregnancy and fetal growth is controlled.
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less