Solving Delivery Of Gene Therapy For Control Of Human Immunodeficiency Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$765,439.00
Summary
Antiretroviral therapy free control of Human Immunodeficiency Virus (HIV) infection requires control of the viral reservoir. We have a unique approach, aimed at enforcing HIV latency by targeting highly conserved regions in the viral promoter. These constructs completely silence viral transcription for long periods of time. We intend to develop & assess vectors that are specifically targeted to the reservoir and which can enforce viral latency despite immune activation or viral variation.
HIV-1 Transcriptional Gene Silencing By Promoter Targeted Si/shRNAs: Uncovering Mechanisms, Optimising Delivery Systems, Assessing In Vivo Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$641,789.00
Summary
Current therapy for HIV is effective but must be taken for life. If therapy is stopped the virus comes back immediately from reservoirs not affected by current drugs. These fluctuating levels of virus are associated with increased illness and death. We are exploring a method of inducing prolonged viral latency using short double stranded RNA molecules. We propose to understand the mechanism of action of these possible therapeutics and to develop these constructs towards use in clinical trials.
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
Redirecting T-cells For Immunotherapy Of Leukaemia And Lymphoma By The Expression Of A CD19-specific Chimeric Antigen Receptor Using The PiggyBac Transposon Gene Modification System
Funder
National Health and Medical Research Council
Funding Amount
$374,876.00
Summary
Most lymphomas respond to therapy but then relapse. Immune cells can attack and kill virus related lymphomas. However, most lymphomas are NOT virus related. We will create immune cells targeting these virus negative lymphomas by inserting artificial receptors into the immune cells. These receptors attach to the lymphoma and activate the immune cells. The immune cells will home to the lymphoma, kill lymphoma cells and persist in the body for many years, preventing lymphoma relapse.
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.
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
On the mechanism of boiling instability in microchannels. This project will enable designers to create highly efficient miniaturised devices based on the boiling of fluids such as water or organics. These devices include micro-power generation systems, coolers for computer chips and solar collectors, and micro-chemical process systems. Such devices provide environmental, safety and economic benefits.
Heat Transfer Characteristics of Biological Tissues with Nanoparticles. Heat transfer of laser-irradiated nanoparticles in biological tissues requires a basic knowledge of the unique strong resonance absorption properties and a fundamental understanding of the thermal and chemical conversions as a consequence of these heated nanoparticles. This project aims to investigate the extent of the non-equilibrium heating effects of heated nanoparticles on the destruction of biological tissues. Comprehen ....Heat Transfer Characteristics of Biological Tissues with Nanoparticles. Heat transfer of laser-irradiated nanoparticles in biological tissues requires a basic knowledge of the unique strong resonance absorption properties and a fundamental understanding of the thermal and chemical conversions as a consequence of these heated nanoparticles. This project aims to investigate the extent of the non-equilibrium heating effects of heated nanoparticles on the destruction of biological tissues. Comprehensive experimental studies and computational modelling to be performed are expected to significantly enhance the understanding of laser-induced heating phenomena of embedded nanoparticles in biological tissues and the prediction of the level of destruction that can be experienced by these heated nanoparticles.Read moreRead less
Time dependent stratified flows in a differentially heated cavity under realistic conditions. Flows driven by the application of a horizontal temperature gradient has applications in nature and engineering. Although much progress has been made in the analysis of the case of a sudden application of temperature differences to the vertical walls of a container with insulating horizontal walls containing an isothermal fluid, the reality is that neither the insulated walls nor the initially isotherma ....Time dependent stratified flows in a differentially heated cavity under realistic conditions. Flows driven by the application of a horizontal temperature gradient has applications in nature and engineering. Although much progress has been made in the analysis of the case of a sudden application of temperature differences to the vertical walls of a container with insulating horizontal walls containing an isothermal fluid, the reality is that neither the insulated walls nor the initially isothermal fluid can be achieved. This project will, by analytical, numerical and experimental methods, make a preliminary investigation of the influence of conducting horizontal walls and an initially stratified fluid.Read moreRead less
Design and Optimisation of Novel Enthalpy Heat Exchangers. This project deals with the thermal design and optimisation of a novel type of latent energy heat exchanger. This new heat exchanger overcomes the practical implementation problems of previous latent energy heat exchangers such as heat-wheels. The main application of this innovative heat exchanger will be to improve the capacity and efficiency of air conditioning systems. As the new heat exchanger is very compact it will be ideally sui ....Design and Optimisation of Novel Enthalpy Heat Exchangers. This project deals with the thermal design and optimisation of a novel type of latent energy heat exchanger. This new heat exchanger overcomes the practical implementation problems of previous latent energy heat exchangers such as heat-wheels. The main application of this innovative heat exchanger will be to improve the capacity and efficiency of air conditioning systems. As the new heat exchanger is very compact it will be ideally suited for integration with air conditioning coils. Existing latent heat wheels are very bulky and are difficult to integrate into standard air conditioner installations.Read moreRead less