Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less
Identifying Novel Antimalarial Targets Using ENU Mutagenesis In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$760,170.00
Summary
Malaria is estimated to cause 1.2 million deaths per year. The malarial parasite has developed resistance to most drugs and new drugs are needed. We aim to mimic the protective red blood cell diseases common in human populations in malarial endemic areas by identifying host targets that are important in parasite growth.
Helping Central Banks Measure Unobserved Variables Using Real-time Forecasts. The project addresses structural measurement problems confronted routinely by central bankers. The techniques developed, and the estimates provided, will aid directly the Partner Organisations (the Reserve Bank of Australia, the Reserve Bank of New Zealand and Norges Bank) and other central banks in formulating monetary policy. The analysis will allow interest rates in Australia and elsewhere to be set with greater pre ....Helping Central Banks Measure Unobserved Variables Using Real-time Forecasts. The project addresses structural measurement problems confronted routinely by central bankers. The techniques developed, and the estimates provided, will aid directly the Partner Organisations (the Reserve Bank of Australia, the Reserve Bank of New Zealand and Norges Bank) and other central banks in formulating monetary policy. The analysis will allow interest rates in Australia and elsewhere to be set with greater precision. The techniques developed in this project will facilitate the understanding and communication of monetary policy within the central banks concerned, and enhance communication of monetary policy strategy to the public.Read moreRead less
Prevalence report by the Australian Advisory Board on Autism Spectrum Disorders (ASD) estimated that 1 child in every 160 children in the 6-12 year-old age group is affected by ASD. There is no cure for ASD and the causes are not understood. We propose that sex hormones may play a role in the development of these disorders. We will test this hypothesis using knockout and transgenic mouse models which have social interaction deficits and brain structure reminiscent of these disorders.
Unraveling ocean mixing and air-sea forcing along the Indo-Pacific exchange. This project aims to collect unprecedented observations and develop high resolution model simulations to examine changes in the Indonesian Throughflow (ITF) north of Australia. This project expects to develop new knowledge of ocean-atmosphere interactions along the path of the ITF from the Pacific to the Indian Ocean, which are the powerhouse that drives changes in winds and rainfall around Australia and the entire Indo ....Unraveling ocean mixing and air-sea forcing along the Indo-Pacific exchange. This project aims to collect unprecedented observations and develop high resolution model simulations to examine changes in the Indonesian Throughflow (ITF) north of Australia. This project expects to develop new knowledge of ocean-atmosphere interactions along the path of the ITF from the Pacific to the Indian Ocean, which are the powerhouse that drives changes in winds and rainfall around Australia and the entire Indo-Pacific region. Expected outcomes include a 1000-fold increase in the observations of mixing in the Indonesian seas and new understanding of the ocean-atmosphere processes that control water property change along the ITF. This should lead to strong improvement in the skill of climate forecast models in the Australian region.Read moreRead less
Coupling tropical cyclone and climate physics with ocean waves. It is argued that without accounting for the wave effects directly, the physics of large-scale air-sea interactions is inaccurate and incomplete. The project will introduce explicit coupling of large-scale atmospheric and oceanic phenomena with the physics of surface waves which should lead to improved predictions of tropical cyclones and climate.
Modeling Human Actin Related Protein 2/3 Complex Subunit 1B (ARPC1B) Deficiency In Mice
Funder
National Health and Medical Research Council
Funding Amount
$755,005.00
Summary
The actin cytoskeleton forms the structure that not only keeps cells in their normal shape but is also essential for the movement of cells and for interaction between cells. We have recently identified the first patients with an immunodeficiency caused by a defect in a gene called ARPC1B, which plays a crucial role in the regulation of actin. Through the investigation of novel mouse models we will elucidate the pathomechanism underlying the disease of these patients.
Cloudiness over the Southern Ocean: reducing a key knowledge gap and source of climate model uncertainty. Southern Ocean clouds are key ingredients of the global climate system and yet are only poorly understood and poorly represented in climate models. Through the use of advanced observational analysis techniques this research will provide a deep understanding of key Southern Ocean cloud regimes and improve their representation in models.
Unsaturation of vapour pressure inside leaves: fundamental, but unknown. This project aims to determine when and to what extent the air inside leaves becomes unsaturated with water vapour. All current interpretation and modelling of leaf gas exchange assumes saturation under all circumstances. Compelling evidence has been obtained that suggests this is not true under moderate air vapour pressure deficits. A novel technique will be employed to assess the water vapour concentration of the air insi ....Unsaturation of vapour pressure inside leaves: fundamental, but unknown. This project aims to determine when and to what extent the air inside leaves becomes unsaturated with water vapour. All current interpretation and modelling of leaf gas exchange assumes saturation under all circumstances. Compelling evidence has been obtained that suggests this is not true under moderate air vapour pressure deficits. A novel technique will be employed to assess the water vapour concentration of the air inside leaves based on stable isotope analysis of carbon dioxide and water vapour exchanged between leaves and air. The project is expected to provide fundamental knowledge about how stomata regulate photosynthesis and water use, with significant implications for modelling vegetation function and for improving the performance of crop plants.Read moreRead less
Global trends in oceanic wind speed and wave height. This project will determine whether winds and waves over the world's oceans have changed over the past 30 years. Such information is critically important in understanding global climate change, evaporation, air-sea interaction and to safely design and operate coastal and offshore facilities.