Inhibition Of Cellcell Actin-based Motility During Poxvirus Infection By The Kinase Inhibitor Glivec
Funder
National Health and Medical Research Council
Funding Amount
$92,950.00
Summary
Although smallpox, one of the deadliest human pathogens, was eradicated in 1980, the current global climate has resulted in fears that smallpox may be used as a biological weapon. Unfortunately the smallpox vaccine poses a serious health hazard to certain people. We have shown that Glivec, a drug used to treat cancer, has potent anti-viral affects on poxvirus replication. This project will test the effectiveness of Glivec in treating smallpox in an animal model and study how it acts.
The Older Australian Twins Study (OATS) Of Healthy Brain Ageing And Age-related Neurocognitive Disorders
Funder
National Health and Medical Research Council
Funding Amount
$940,960.00
Summary
Ageing is associated with cognitive decline and dementia. It is still not completely understood what relative contributions genes and environment play in these. This project is an extension of the Older Australian Twins Study to examine genetic and environmental factors associated with late life brain changes and dementia, and will establish an internationally significant cohort for novel discovery.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dy ....What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dying from viruses; however, it is not known what is cause and effect. This project will clarify Varroa’s exact role in the evolution of virulence in RNA viruses. The intended outcome is increased knowledge allowing the design of an effective treatment to prevent the death of honeybee colonies.Read moreRead less
Molecular Regulation Of CRH Gene Expression In The Human Placenta
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormon ....Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely the rise in CRH production occurs earlier and more rapidly, while in women who deliver late the rise occurs more slowly. This work has led to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done by examining the DNA sequences involved in controlling the CRH gene and by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and preterm birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be developed.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
Integrating nutritional immunology. What an organism eats affects both its susceptibility to disease and the community of beneficial microorganisms living within its gut. This project will study how nutrition, immunity and the flora of the gut interact, and whether hosts are able to select a diet that optimises their immune response and gut flora in the face of disease challenges.
Imaging The Hepatitis C Virus Life Cycle In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may unco ....Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may uncover novel therapeutic strategies to combat HCV.Read moreRead less
Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the poten ....Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the potential impact that these viral invasions had on the evolutionary development of their ancestral hosts will be investigated. This could facilitate previously unattainable insights into both AAV and marsupial evolution, with broader implications relevant to the advancement of the fields of virology and mammalian evolution.Read moreRead less
BRIDGET: BRain Imaging, Cognition, Dementia And Next Generation GEnomics: A Transdisciplinary Approach To Search For Risk And Protective Factors Of Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,081,489.00
Summary
Alzheimer’s disease (AD) begins many years before diagnosis and yet its aetiology is still poorly understood. The BRIDGET consortium aims to identify genetic variants that are associated with structural brain ageing, cognitive performance, and dementia risk in richly phenotyped international and Australian population-based samples. This work aims to provide crucial information on the molecular pathways leading to AD, potentially leading to improved health outcomes for our ageing population.