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.
Age-and Species-related Regulation Of Host Inflammatory Responses In Falciparum And Vivax Malaria
Funder
National Health and Medical Research Council
Funding Amount
$323,640.00
Summary
Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines ....Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines for adults and children.Read moreRead less
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.
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.
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.
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.
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.
Host-pathogen Interactions In Burkholderia Infection
Funder
National Health and Medical Research Council
Funding Amount
$490,322.00
Summary
Melioidosis is a fatal tropical disease caused by a bacterium Burkholderia pseudomallei. We found that when the bacterium infects macrophage-like cells in culture (that normally kills bacteria), the cells turn into a cell like an osteoclast, a cell that normally degrades bone. Since an osteoclast is unable to kill bacteria, we speculate that the bacterium subverts the macrophage differentiation pathway and directs the cells into a state where it is unable to attack the invading bacteria.