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 Role Of Chemokines In Establishing HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Although antiviral therapy is effective in controlling HIV, therapy must be continued life-long because the virus cannot be cleared from long lived infected CD4+ T cells that are silently or latently infected. In this proposal we will explore the mechanism of how HIV can enter these resting CD4+ T-cells and establish long lived latent infection. Understanding this process may potentially lead to new strategies to cure HIV infection.
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.
Refining And Testing A Promising New Treatment For Chronic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$743,947.00
Summary
Chronic pain costs Australia about 35 billion dollars a year. Recent scientific discoveries show that treatment aimed at correcting problems in how the brain processes sensory input can reduce pain and disability. This project will clarify some key aspects of these problems and use that information to make final adjustments to an already very promising treatment. We will then test the treatment in a definitive and comprehensive clinical trial.
Galectin-3 And Phagocyte Function In Severe Asthma
Funder
National Health and Medical Research Council
Funding Amount
$698,084.00
Summary
Asthma, a major chronic inflammatory disease affects more than 2 million Australians. Neutrophilic severe asthma is not responsive to current therapies. We have recently made a significant advance in understanding neutrophilic asthma, reporting low levels of a protein called galectin-3 (gal-3). In this project we will explore the role of gal-3 its effect on the resolution of inflammation. This study will result significantly advance the knowledge of the mechanisms of neutrophilic severe asthma.
Centre For Clinical Research Excellence In Respiratory And Sleep Medicine
Funder
National Health and Medical Research Council
Funding Amount
$2,200,000.00
Summary
The CCRE will enhance Australia's international research reputation in clinical respiratory and sleep medicine by enhancing links between hospital-based investigators. This will foster development of new clinical researchers in these fields. Major research projects will include reducing side effects of asthma therapy in the elderly, better and cheaper ways of diagnosing disorders such as sleep apnoea and blood clots in the lung, keeping patients with chronic lung diseases out of hospital and avo ....The CCRE will enhance Australia's international research reputation in clinical respiratory and sleep medicine by enhancing links between hospital-based investigators. This will foster development of new clinical researchers in these fields. Major research projects will include reducing side effects of asthma therapy in the elderly, better and cheaper ways of diagnosing disorders such as sleep apnoea and blood clots in the lung, keeping patients with chronic lung diseases out of hospital and avoiding accidents due to lack of sleep.Read moreRead less
Combating Escalating Harms Associated With Pharmaceutical Opioid Use
Funder
National Health and Medical Research Council
Funding Amount
$925,767.00
Summary
Increases in opioid use have been accompanied by increased opioid harms. But there is a lack of population-level evidence about drivers of long-term prescribed opioid use, dependence, overdose and other harms. Using linked data, we will fill these gaps using a cohort of all people in NSW prescribed opioids since 2002, linked to datasets containing information on health, social and health service utilisation, that will permit a comprehensive assessment of the risks of all prescribed opioids.
Improving Health Outcomes In The Tropical North: A Multidisciplinary Collaboration
Funder
National Health and Medical Research Council
Funding Amount
$5,997,916.00
Summary
Improving Health Outcomes in the Tropical North will strengthen partnerships with research institutions in the NT, Qld, WA, NSW, Vic and SA, by undertaking a research agenda that will help close the gap in Indigenous health disadvantage, protect the north from emerging infectious threats and engage regional neighbours. We will establish a northern Australian network that incorporates Indigenous engagement, mentoring and knowledge translation, and facilitates collaboration with southern partners.
Understanding Persistent Low Back Pain Where It Resides, In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$848,972.00
Summary
Low back pain is a leading cause of disability amongst Australians. A critical question is why some people get better after hurting their back while others do not. This project examines whether changes in the brain predict low back pain outcome. This information will rapidly advance our understanding of low back pain and has the potential to facilitate the development of novel therapies.