Cellular Microenvironments Facilitating The Replication And Propagation Of Flaviviruses
Funder
National Health and Medical Research Council
Funding Amount
$505,279.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus a ....Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus as a model, and advanced techniques in biochemistry and electron microscopy, we have identified for the first time these membrane structures as the apparent sites of replication of the viral RNA or genetic material, and of the viral proteins involved. We have also observed how new virus particles are able to get out of infected cells and shown how some drugs can prevent this occurring thus limiting their transmission. This research will focus on how the membrane structures are formed in infected cells. The research will determine what cellular components are required by the virus to help it propagate. In particular specific cellular proteins and membrane components that are captured by the virus and moved to different sites in the infected cells. These apparent requirements could possibly lead us to a greater understanding of the complex interactions that occur between the invading virus and the host cells. We aim to directly visualize the process of infection within living cells using new and innovative microscopic techniques. Another of our objectives is to determine the effects of infection on normal cells. The question being whether flavivirus infection disrupts normalcell fuctions like secretion etc. An understanding of these processes, and how the viral RNA is copied into new RNA for more virus particles, will assist in the development of antiviral drugs for treatment of this pathogenic group of viruses.Read moreRead less
Differences In Neonatal Immune Regulation In The Developing And Developed World: Implications For Neonatal Vaccinations?
Funder
National Health and Medical Research Council
Funding Amount
$332,083.00
Summary
This project will study the effect of adverse living conditions such as high microbial exposure, malnutrition, environmental tobacco smoke and malaria infection on the development of a newborn's immune system,by comparing immune response between newborns in Papua New Guinea and in Western Australia. This study will help us to understand the high susceptibility of children in the developing world for infectious diseases and to develop better prevention strategies.
This study combines sophisticated molecular techniques with state-of-the-art biochemical and physiological analyses to determine how gut hormones regulate satiety. By utilising unique conditional and germline KO mice , this research will make highly original and internationally competitive contributions to the understanding of the regulation of satiety and energy expenditure. Knowledge as to the causes of lack of satiety will be of great benefit in the search for novel treatments for obesity.
Modulation Of Apoptosis By Cytomegalovirus: Analysis Of New Mechanisms To Interfere With Cytomegalovirus-induced Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,084.00
Summary
Apoptosis, or programmed cell death is an essential process in developmental and homeostatic control of complex biological systems. In addition to these primary house keeping roles, apoptosis provides a powerful defence mechanism against invading pathogens, such as viruses, since it allows early elimination of infected cells from the host. A basic property of herpesviruses is their ability to establish persistent infection and remain in association with the host for its lifetime. This strongly u ....Apoptosis, or programmed cell death is an essential process in developmental and homeostatic control of complex biological systems. In addition to these primary house keeping roles, apoptosis provides a powerful defence mechanism against invading pathogens, such as viruses, since it allows early elimination of infected cells from the host. A basic property of herpesviruses is their ability to establish persistent infection and remain in association with the host for its lifetime. This strongly underlines their success at reaching an accommodation with the immune system's anti-apoptotic mechanisms. The central hypothesis of this project is that herpesviruses, such as murine and human cytomegalovirus, encode proteins that interfere with cell death pathways thereby circumventing host defence so that viral replication and dissemination can proceed. Thus, the aims are to identify and characterise cytomegalovirus proteins that modulate apoptosis. These studies will improve our understanding of the control of apoptosis during viral infection, especially as caused by cytomegaloviruses. Human cytomegalovirus (HCMV) is a pathogen able to cause significant morbidity and mortality in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. Hence, the proposed studies will allow the elucidation of molecular mechanisms that may be relevant to the pathogenesis of HCMV in man and will provide insights into the rational design of suitable antiviral drugs and vaccines. Understanding viral mechanisms of host immune evasion continues to improve our understanding of complex cellular pathways. Therefore, given that abnormal regulation of apoptosis is implicated in the development of degenerative conditions, cancer and autoimmune disease, the proposed studies will provide valuable insight towards the development of new therapies for these pathological conditions.Read moreRead less