Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
Identifying Key Players In The Spread Of Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$817,448.00
Summary
Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australi ....Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australia.Read moreRead less
Synchrotron X-ray Assessment Of Airway Surface Physiology For Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$778,228.00
Summary
We seek a cure or long-lasting therapy for the fatal airway disease in cystic fibrosis. Disease is caused by a shallow and dehydrated airway surface liquid (ASL), allowing bacteria to infect the lung. We can introduce a corrective gene into mouse airways where it can be effective for over 1 yr, but no fast, accurate and non-invasive measurement exists to test if treatments are successful. We will develop methods using synchrotron light to directly measure ASL depth changes in live mouse airways.
Assessment of the new technologies to maximise the internal energy efficiency by modelling the energy flows in Victorian power stations. Increased internal energy efficiency will reduce the CO2 emissions and increase the profit margin for the power stations. The aim of the proposed research is to investigate the internal energy efficiency in the brown coal fired power stations by modelling the internal energy flows to reveal the potentials in the 'waste' heat streams in the power stations, and t ....Assessment of the new technologies to maximise the internal energy efficiency by modelling the energy flows in Victorian power stations. Increased internal energy efficiency will reduce the CO2 emissions and increase the profit margin for the power stations. The aim of the proposed research is to investigate the internal energy efficiency in the brown coal fired power stations by modelling the internal energy flows to reveal the potentials in the 'waste' heat streams in the power stations, and to assess new waste heat recovery measures for the power industry. The proposed research, supported by the entire Victorian power generation industry, will help the industry to achieve their green house gas emission reduction target set by the Federal Government.
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Horizontal convection at ocean-relevant proportions. This project aims to determine the role of buoyancy differences from solar radiation and vertical confinement. Flows created by lateral variation in heat or buoyancy are poorly understood when the horizontal length greatly exceeds the height, precisely the conditions relevant to industry and understanding the role of horizontal convection in Earth's oceans and in turn the delicate current system that maintains Earth's temperate climate. This p ....Horizontal convection at ocean-relevant proportions. This project aims to determine the role of buoyancy differences from solar radiation and vertical confinement. Flows created by lateral variation in heat or buoyancy are poorly understood when the horizontal length greatly exceeds the height, precisely the conditions relevant to industry and understanding the role of horizontal convection in Earth's oceans and in turn the delicate current system that maintains Earth's temperate climate. This project proposes computational and experimental efforts to probe the ultimate regime of heat transport in very shallow horizontal convection, benefiting humankind through improvements to future ocean and climate modelling efforts.Read moreRead less
The elusive upper bound of heat transfer in horizontal convection. The question as to whether lateral variation in global ocean buoyancy resulting from low solar radiation near the poles and higher temperatures in the tropical regions (known as horizontal convection) is a driver for global ocean currents is critical to our understanding of this complex and delicate system that maintains Earth's temperate climate. This question hinges on the relationship between heat transport and strength of buo ....The elusive upper bound of heat transfer in horizontal convection. The question as to whether lateral variation in global ocean buoyancy resulting from low solar radiation near the poles and higher temperatures in the tropical regions (known as horizontal convection) is a driver for global ocean currents is critical to our understanding of this complex and delicate system that maintains Earth's temperate climate. This question hinges on the relationship between heat transport and strength of buoyancy forcing towards global scales; this project proposes a landmark experimental effort supported by detailed simulations to probe the ultimate regime of heat transport in horizontal convection. The project is expected to inform the direction of future ocean and climate modelling efforts to the benefit of humanity.Read moreRead less
Simulating two-phase electrodynamic flows in droplet-based microfluidic circuit elements. The knowledge, data and analysis tools developed within this project will facilitate the economical production of electrodynamically controlled integrated droplet-based microfluidic devices for critical high-demand applications such as: genome sequencing; protein evolution, synthesis and crystallisation; micro-structured pharmaceuticals; disposable devices for biomedical analysis; portable point-of-entry (b ....Simulating two-phase electrodynamic flows in droplet-based microfluidic circuit elements. The knowledge, data and analysis tools developed within this project will facilitate the economical production of electrodynamically controlled integrated droplet-based microfluidic devices for critical high-demand applications such as: genome sequencing; protein evolution, synthesis and crystallisation; micro-structured pharmaceuticals; disposable devices for biomedical analysis; portable point-of-entry (biochem)security analysis devices. Hence this project is an investment in enabling technologies to benefit Australia's growing biotech, pharmaceutical and micro/nanotechnology sectors. Tangible community benefits (e.g., in improved diagnostic technologies, pharmaceuticals) will result.Read moreRead less
Process scalability and performance prediction of Viscous Transfer Micro Turbines for use as miniaturised power supplies. This project aims to predict the performance and scalability of viscous transfer turbines. The work will be carried out with Micromachines Ltd., a firm developing working turbines with 50 mm rotors. The goal of the research is to gain an understanding of the scaling laws for these turbines, in order to predict their performance. Viscous transfer turbines have a very simple di ....Process scalability and performance prediction of Viscous Transfer Micro Turbines for use as miniaturised power supplies. This project aims to predict the performance and scalability of viscous transfer turbines. The work will be carried out with Micromachines Ltd., a firm developing working turbines with 50 mm rotors. The goal of the research is to gain an understanding of the scaling laws for these turbines, in order to predict their performance. Viscous transfer turbines have a very simple disc construction making them ideal for manufacturing as small-scale units (with a 5 mm rotor). Small enough to replace batteries, but with a higher power output, they would provide the need for higher power output devices to replace batteries.Read moreRead less
Integrating Immunity And Genetics In Follicular Lymphoma To Establish A Prognostic Score Fit For The Modern Era
Funder
National Health and Medical Research Council
Funding Amount
$1,377,174.00
Summary
Follicular lymphoma (FL) is divided into early and advanced stages. Early stage FL is frequently cured, but there is no way to identify who will be cured and who won't. By contrast advanced stage FL is incurable. Our unique access to well-annotated clinical trial and population based cohorts allows us to perform a detailed biological comparison of early and advanced FL, to gain a deeper understanding of the impediments to eradicating the disease, and to predict outcome to conventional therapy.
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