Mechanisms Of Immune Modulation By Human Cytomegalovirus During The Latent Phase Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$165,500.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. CMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Bone marrow and solid organ transplant recipients are particularly at risk of developing serious CMV disease. CMV has the remarkable ability to hide in the body in a dormant or latent form for the life of the host. However, when conditions are right the virus can awaken (ie reactivate) from its ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. CMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Bone marrow and solid organ transplant recipients are particularly at risk of developing serious CMV disease. CMV has the remarkable ability to hide in the body in a dormant or latent form for the life of the host. 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 reactivation from latency is of most medical significance, yet the latent phase of infection remains very poorly understood. We recently reported that during latent infection CMV interfered with the expression of a protein which plays a crucial role in our immune system. This protein is called MHC class II and its proper function is essential for our immune system to fight infections. Thus, we postulated that the ability of CMV to successfully hide in a cell in a latent state is at least partially due to its ability to interfere with the cells ability to properly make MHC class II proteins. This project aims to futher define and characterise the functions of latent CMV that enable it to interfere with our immune system. Firstly, we aim to continue with our studies to determine the mechanism by which latent CMV interferes with MHC class II expression. Secondly, we will seek to determine whether latent CMV interferes with any other important components of our immune system. Thirdly, we will seek to identify the precise viral gene that causes the interference with MHC class II expression. Determining the mechanism of immune system regulation and the viral gene(s) responsible for this interference may lead to the design of gene therapies to lessen the clinical impact of CMV disease in transplant recipients.Read moreRead less
Human Cytomegalovirus Gene Expression And Functions During Latent Infection And Reactivation
Funder
National Health and Medical Research Council
Funding Amount
$789,473.00
Summary
Human cytomegalovirus has the ability to hide in the body in a latent form for the life of the host. However, the virus can awaken (reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed people such as transplant patients that reactivation from latency causes significant morbitity and mortality, yet the latent infection remains very poorly understood. This project will identify and define the functions of viral genes that facilitate latency.
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
Molecular & Translational Characterisation Of IMiD-Mediated BET-Protein Degradation In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$497,857.00
Summary
Thalidomide-like drugs (called IMiDs) are an essential treatment for multiple myeloma, a common incurable blood cancer. We have discovered that IMiDs destroy proteins that myeloma cells use to ‘read’ cancer-causing genes in their own DNA. We will therefore investigate how important the destruction of these ‘gene readers’ is in myeloma cells, including patient samples. This will set up future studies targeting ‘gene readers’ using IMiDs in combination with other targeted drugs in clinical trials.
Building A Bridge Between Animal Models Of Blood Transfusion And Clinical Practice: Development Of Sheep Laboratory Models To Investigate The Effects Of Transfusion
Funder
National Health and Medical Research Council
Funding Amount
$86,117.00
Summary
This research project aims to develop clinically-relevant sheep laboratory models of transfusion that will provide a ‘bridge’ between human laboratory and sheep in vivo models and clinical setting by contributing to a better understanding of the underlying mechanisms of transfusion with stored blood products. Ultimately, addressing key knowledge gaps regarding transfusion of aged and cryopreserved blood products will result in improved outcomes for patients.
Genes Of Mycobacterium Tuberculosis Essential For Latent Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
One third of the worlds population is latently infected with M. tuberculosis, the bacteria which causes TB. We have identified key genes in M. tuberculosis that enable the bacterium to shut-down and become latent. This project will investigate these genes, identify their role and yield vital information for a new paradigm of drug and vaccine development. Improved vaccines and drugs which can target and inhibit latency would be of enormous benefit to the global community.