New Mechanisms Of Immunomodulation By Interferon Transsignaling
Funder
National Health and Medical Research Council
Funding Amount
$540,441.00
Summary
The aim of this project is to characterise a new discovery of how the body can regulate its response to disease such as infections and cancer. Interferons are produced by the body to stimulate immune reactions to these diseases. We have dicovered that a circulating form of an interferon binding protein or receptor can change the nature of an immune response. We plan to study how this is achieved and whether this information can be used therapeutically.
NOD1 Sensing Of H. Pylori Peptidoglycan Promotes Cell Survival And Bacterial Persistence
Funder
National Health and Medical Research Council
Funding Amount
$792,492.00
Summary
The bacterium H. pylori lives in the stomach of half the world’s population and is a major cause of human disease, including peptic ulcers and stomach cancer. This project will investigate how H. pylori is able to manipulate the host immune system by modifying the composition of its outside layer (the cell wall). In so doing, H. pylori causes changes in cells of the stomach lining that allow the bacterium to persist, but that also may predispose the host to cancer.
We seek to gain a detailed understanding of how interactions between the West Nile virus proteins and host factors involved in the IFN response determine the outcome of virus infection. Better understanding of the mechanisms employed by this highly pathogenic virus to disable the mammalian host's IFN response will have wider implications for our understanding of other human diseases such as cancer, autoimmunity and provide new avenues for design of efficient antiviral and anticancer therapies.
Toxoplasma Gondii Infection Of Human Retinal Pigment Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$460,668.00
Summary
Ocular toxoplasmosis is a vision-threatening parasitic eye infection that is common in Australia and worldwide. No treatment cures the disease. This work will characterize cellular and molecular events occuring in the eye during an infection, which is an important first step toward the development of more effective treatments for patients with the condition.
Several members of the Flaviviridae family are major pathogens of humans including dengue (DEN), yellow fever (YF), tick-borne encephalitis (TBE), Murray valley encephalitis (MVE), Japanese encephalitis (JE), and hepatitis C virus (HCV). An Australian flavivirus Kunjin (KUN), however, appears to be naturally attenuated and does not cause an overt disease in humans. In contrast, genetically and antigenically closely related to KUN, New York strain of West Nile virus (NY WN) has already caused ~50 ....Several members of the Flaviviridae family are major pathogens of humans including dengue (DEN), yellow fever (YF), tick-borne encephalitis (TBE), Murray valley encephalitis (MVE), Japanese encephalitis (JE), and hepatitis C virus (HCV). An Australian flavivirus Kunjin (KUN), however, appears to be naturally attenuated and does not cause an overt disease in humans. In contrast, genetically and antigenically closely related to KUN, New York strain of West Nile virus (NY WN) has already caused ~500 deaths and over 20,000 registered infections since its emergence in North America in 1999, including 223 deaths and 9122 infections in 2003 alone. Recent studies with DEN indicated that flaviviruses may interfere with early steps of IFN-signalling pathway. The type I Interferon (IFN) response is the first line of defence against viral infections and many viruses have developed different strategies to counteract this response in order to ensure their survival in the infected host. In this grant we seek to exploit our extensive understanding of the molecular biology of KUN virus and the contrasting behaviour of KUN and NY WN viruses to gain an understanding of the role of flavivirus-mediated suppression of host anti-viral IFN response in virus-host relationships and its importance in determining virus virulence.Read moreRead less
Host-directed Therapy For Malaria: Host Cell Signalome As A Target
Funder
National Health and Medical Research Council
Funding Amount
$898,043.00
Summary
Malaria parasites kill 450,000 children a year and impact on the economic development of communities. Spreading drug resistant malaria parasites within Australia's South-East Asian neighbours creates an urgent and unmet need for new drug treatments. We will characterise host signals required for parasite survival in immature erythrocytes and identify host-directed, ready to develop, resistance-proofed drugs to kill malaria parasites.