Deciphering Mechanisms Of Liver Allograft Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$520,964.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Liver transplants are more readily accepted than other organ grafts in the absence of immunosuppressive drugs but little is known about the mechanisms that prevent an effective response. This proposal aims to unravel these mechanisms. This project will have important implications for transplantation studies.
Analysis Of Viral And Cellular Gene Expression During Human Cytomegalovirus Latent Infection Of Hematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body a ....Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.Read moreRead less
Viral And Host Cell Gene Expression During The Establishment And Maintenance Phases Of Human Cytomegalovirus Latency
Funder
National Health and Medical Research Council
Funding Amount
$149,250.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.Read moreRead less
The effect of tunelling on existing rock bolts. As more underground facilities such as rail, road, sewerage and service tunnels are constructed in our major cities, more and more frequently new tunnels have to cross over or run alongside existing tunnels. As the roofs of tunnels are generally supported by rock bolts and lined with shotcrete, the support system can be damaged by the rock movements caused by the excavation of the new tunnel. Little research has been carried out on this problem, an ....The effect of tunelling on existing rock bolts. As more underground facilities such as rail, road, sewerage and service tunnels are constructed in our major cities, more and more frequently new tunnels have to cross over or run alongside existing tunnels. As the roofs of tunnels are generally supported by rock bolts and lined with shotcrete, the support system can be damaged by the rock movements caused by the excavation of the new tunnel. Little research has been carried out on this problem, and so often expensive deviations have to be made to tunnels to avoid going near existing ones. The proposed research will provide numerical tools to allow prediction of loads induced into rock bolts by nearby tunnels, leading to more economical and safer tunnel design.
Read moreRead less
Enhanced Analysis of Time Dependent Viscous Behaviour of Soft Clay. Often post construction settlements of structures overlying clayey soils have been observed to be more than those predicted, or the predicted rate of settlement is not correct. The main benefit of this research is providing an accurate but simplified approach, which can be used by practicing engineers to predict the post construction settlement of structures in the design phase of construction projects. The community can conside ....Enhanced Analysis of Time Dependent Viscous Behaviour of Soft Clay. Often post construction settlements of structures overlying clayey soils have been observed to be more than those predicted, or the predicted rate of settlement is not correct. The main benefit of this research is providing an accurate but simplified approach, which can be used by practicing engineers to predict the post construction settlement of structures in the design phase of construction projects. The community can considerably benefit from the findings of this project including safer structures, significant reduction in the future maintenance costs and enhancing the performance of bridges, buildings, roads, railways and dams with less cracks and differential settlement.Read moreRead less
Progressive liquefaction within marine sediments: comparison between geo-centrifuge modelling, full-scale wave tank tests and numerical modelling. The evaluation of wave-induced liquefaction within the marine sediment is particularly important for coastal and geotechnical engineers involved in the design of foundation around coastal structures. The proposed study will integrate the existing knowledge from the aspects of coastal and geotechnical engineering with that of overseas experts to provid ....Progressive liquefaction within marine sediments: comparison between geo-centrifuge modelling, full-scale wave tank tests and numerical modelling. The evaluation of wave-induced liquefaction within the marine sediment is particularly important for coastal and geotechnical engineers involved in the design of foundation around coastal structures. The proposed study will integrate the existing knowledge from the aspects of coastal and geotechnical engineering with that of overseas experts to provide coastal engineers with an effective tool for the design of foundations around marine structures. It will also assist in reducing the risk of potential environmental damage caused by failure of marine structures.Read moreRead less
Time-dependent dynamic, creep and shrinkage response of curved structural members. This project concerns curved structural members, such as bridge beams, that are subjected to dynamic excitation and to concrete shrinkage and creep. Hitherto, unified formulations for the structural behaviour of these members have not been properly developed. The proposal seeks to build on a previous ARC DP of the investigator that produces significant results for static loading, by developing a sophisticated meth ....Time-dependent dynamic, creep and shrinkage response of curved structural members. This project concerns curved structural members, such as bridge beams, that are subjected to dynamic excitation and to concrete shrinkage and creep. Hitherto, unified formulations for the structural behaviour of these members have not been properly developed. The proposal seeks to build on a previous ARC DP of the investigator that produces significant results for static loading, by developing a sophisticated methodology to handle non-static dynamic loading and for shrinkage and creep. It will develop advanced mathematical tools to enable the safe and efficient design of a multiplicity of structures that is of benefit to on and offshore Australian technology.Read moreRead less
Mathematical and mechanical modeling of nano particulate flow. Nano particulates are the basis for many new technologies, including coatings in the electronics industry, composite materials and medical and pharmaceutical applications. Worldwide industrial competition is increasingly determined by our capacity to handle such highly cohesive materials, and to exploit their novel physical, chemical and mechanical characteristics. Devising handling mechanisms and understanding nano particulate flows ....Mathematical and mechanical modeling of nano particulate flow. Nano particulates are the basis for many new technologies, including coatings in the electronics industry, composite materials and medical and pharmaceutical applications. Worldwide industrial competition is increasingly determined by our capacity to handle such highly cohesive materials, and to exploit their novel physical, chemical and mechanical characteristics. Devising handling mechanisms and understanding nano particulate flows depends on formulating accurate mathematical models which reflect the correct underlying physics. This APF proposal will utilise advanced continuum mechanics to develop the correct underlying conceptual ideas to resolve fundamental nanomechanical particulate flows, which will lead to the next generation of engineering tools.
Read moreRead less
Computational fracture analysis of structures and materials. This project aims to develop a computer simulation technique to address the safety of engineering structures. A novel numerical framework based on the scaled boundary finite element method will be developed to model the fracture process critical to assessing structural integrity. The expected outcomes of this project include an innovative technology for numerical simulation and improved capabilities to generate high-fidelity predictio ....Computational fracture analysis of structures and materials. This project aims to develop a computer simulation technique to address the safety of engineering structures. A novel numerical framework based on the scaled boundary finite element method will be developed to model the fracture process critical to assessing structural integrity. The expected outcomes of this project include an innovative technology for numerical simulation and improved capabilities to generate high-fidelity predictions of structural safety at minimum human efforts. The fully automatic and robust numerical tool developed in this project will help engineers and government authorities to perform safe and cost-effective design and management of engineering structures that are vital to modern economies.Read moreRead less
Geotechnical characterisation of compacted ground based on passive ambient noise techniques. The proposed research will provide our local construction and mining industries with a much needed fast and low cost technology for geotechnical investigation of very large sites which is currently not available. The project will help steer Australia to the forefront of ambient noise research for geotechnical site investigation, in the characterisation of unsaturated compacted soil and in the determinati ....Geotechnical characterisation of compacted ground based on passive ambient noise techniques. The proposed research will provide our local construction and mining industries with a much needed fast and low cost technology for geotechnical investigation of very large sites which is currently not available. The project will help steer Australia to the forefront of ambient noise research for geotechnical site investigation, in the characterisation of unsaturated compacted soil and in the determination of dynamic site characteristics which are required for seismic risk assessment. Two postgraduate students will benefit from this research by receiving research training at the highest level and it will also pave the way for exporting the technology developed overseas, particularly to our near neighbours in Asia and the Pacific. Read moreRead less