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.
Regulation Of Subcellular Localisation Of Respiratory Syncytial Virus M Protein: Implications For Pathology
Funder
National Health and Medical Research Council
Funding Amount
$580,195.00
Summary
Respiratory syncytial virus (RSV) is the major cause of viral pneumonia in infants and the elderly, causing more deaths in winter than influenza. We have observed RSV M protein in the nucleus of infected host cells where it inhibits host cell transcription. We propose to investigate the regulation of nuclear localisation of M by phosphorylation and binding to cellular factors and its importance to RSV pathogenesis. The results will relate strongly to future drug and vaccine development.
The Role Of Subgenomic Non-coding Viral RNA In Flavivirus Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Flaviviruses are transmitted by insects and pose a serious health threat to the Australian population. They can cause fever syndromes, encephalitis and death. We aim at better understanding of how these viruses cause disease. We are particularly interested in elucidating the role of small non-coding nucleic acid produced by flaviviruses in the viral pathogenicity. Ultimately, this deeper understanding should lead to the development of effective vaccines and antiviral therapies.
Structural Characterization Of Novel AB5 Cytotoxin - SubAB
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
AB5 toxins are virulence factors from a range of pathogenic bacteria, including Shiga toxigenic E. coli (STEC), S. dysenteriae, V. cholerae, and B. pertussis. AB5 toxins comprise a catalytic A subunit that disrupts distinct essential cellular processes within the cell and a receptor binding, pentameric B subunit that enables the toxin to target certain cell types. We are structural characterizing a novel AB5 toxin that targets an essential component of the cellular machinery.
Scabies is caused by microscopic mites burrowing through the skin, causing intense itching and providing prime breeding sites for bacteria. The resulting skin sores are very common among Aboriginal children in Australia leading to extreme levels of rheumatic fever-heart disease and renal failure in Indigenous communities. We have discovered mite products termed Serpins which interfere with the patients defence against the mites and the bacteria and aim to develop therapeutics.
Characteristics And Mechanisms Of Persistent Asthma After Common Cold Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$407,750.00
Summary
Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma, and despite a fall in asthma deaths, large number of people continue to have severe attacks requiring hospitalisation. In most cases the deterioration in asthma symptoms is related to a cold or flu like illness. Viruses are the leading cause of these infections and are known to make asthma symptoms worse. We have identified how viruses do this b ....Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma, and despite a fall in asthma deaths, large number of people continue to have severe attacks requiring hospitalisation. In most cases the deterioration in asthma symptoms is related to a cold or flu like illness. Viruses are the leading cause of these infections and are known to make asthma symptoms worse. We have identified how viruses do this by triggering a type of inflammation in the airways. We have also found that after a severe attack of asthma some people do not recover completely. They appear to have persistent problems, and in some cases the virus can still be isolated from the airways. How and why this occurs is not known. We are seeking to understand this problem and describe how it affects people with asthma. We plan to investigate what effect certain viruses have on the lungs of people with asthma by measuring cells and chemicals that are present in sputum. We will use recently developed technologies to accurately see what viruses are infecting these people, and how the immune system is working. This study will shed important light on potential causes of unstable asthma and the role that viral infection plays in this. It may also lead to new opportunities to develop treatments that are more effective in preventing and controlling asthma.Read moreRead less
Hepatitis C affects between 1-3% of Australians. Currently, there is no effective vaccine and only 30% will spontaneously clear infection, while the remained develop a chronic disease with a small risk of progression to liver cirrhosis and liver cancer over time. This study aims to evaluate the safety and efficacy of a two different treatment regimens among individuals with recent Hepatitis C infection; and define the risk factors and natural history of Hepatitis C superinfection during treatmen ....Hepatitis C affects between 1-3% of Australians. Currently, there is no effective vaccine and only 30% will spontaneously clear infection, while the remained develop a chronic disease with a small risk of progression to liver cirrhosis and liver cancer over time. This study aims to evaluate the safety and efficacy of a two different treatment regimens among individuals with recent Hepatitis C infection; and define the risk factors and natural history of Hepatitis C superinfection during treatment.Read moreRead less
Transcriptome Characterization Of Klebsiella Pneumoniae During Infection (TRACKIN)
Funder
National Health and Medical Research Council
Funding Amount
$348,806.00
Summary
Klebsiella pneumoniae (KP) is an important pathogen associated with high mortality and antimicrobial resistance. Upon infection, the host activates a sophisticated immune response, but there is evidence that KP is capable of modifying this response. Here I will take advantage of cutting-edge genome sequencing to understand the interactions between KP and host immunity. These studies will provide a pathway for the development of new therapeutic strategies to combat multiresistant infections.
Understanding Dendritic Cell Dysfunction And Apoptosis In Malaria In Endemic Populations
Funder
National Health and Medical Research Council
Funding Amount
$493,179.00
Summary
The Asia-Pacific has 40% of the global malaria burden, and both major malaria species (falciparum & vivax) cause disease and death. To eliminate malaria we need to understand how malaria parasites prevent our body making new immune responses. Our experienced team will measure how and when the two major malaria parasites switch off and kill specialised immune cells, when immune cells recover after antimalarial therapy and may suggest the need for malaria drugs to be given before immunisations.
The Impact Of Influenza A Virus PB1-F2 Protein On Host Immunity And The Potential For Therapeutic Targeting
Funder
National Health and Medical Research Council
Funding Amount
$317,076.00
Summary
The 1918 influenza virus pandemic resulted in 50 million deaths globally and there is potential for new pandemics, such as the predicted H5N1 Bird Flu . Exact causes of such devastating lethality are not fully identified. Newly discovered influenza A virus (IAV) PB1-F2 protein is present in nearly all highly pathogenic IAVs and promotes virus virulence. This study will further examine the way in which PB1-F2 impacts the host, revealing potential therapeutic targets to lessen disease burden.