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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
Dysregulation Of Cytokine Networks: A Key Determinant Of The Pathogenesis Of Cerebral Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$480,989.00
Summary
Malaria is a parasitic disease that kills some 2 million people each year. It affects the Australian region, e.g. PNG and SE Asia. One of the most serious complications is cerebral malaria (CM). It affects the brain and is often fatal. This project will show whether the early meeting of the malaria parasite with the host's immune system determines if the infection will be a mild, resolving one or a severe, possibly lethal one causing CM. This is highly relevant to vaccine development strategies.
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
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.
Understanding the biology of reactive oxygen species. This project will utilise forefront technologies to identify and characterise fundamental biological processes involving toxic free radicals that cause infectious disease and cancer. The approach synergises with researchers across disciplines and universities to ultimately identify future drugs to improve and maintain health.
Role Of Nucleocytoplasmic Trafficking Of Matrix Protein In RSV Infection
Funder
National Health and Medical Research Council
Funding Amount
$495,041.00
Summary
Respiratory syncytial virus (RSV) is the major cause of viral pneumonia in infants and young children throughout the world. By the age of 3, virtually every child has been infected by RSV at least once. RSV is also an important cause of pneumonia in the elderly and is estimated to cause more deaths each winter than influenza. In Australia, an estimated 100,000 infants are infected by RSV every year. In Victoria, RSV is the most common cause of all reported cases of respiratory tract disease, wit ....Respiratory syncytial virus (RSV) is the major cause of viral pneumonia in infants and young children throughout the world. By the age of 3, virtually every child has been infected by RSV at least once. RSV is also an important cause of pneumonia in the elderly and is estimated to cause more deaths each winter than influenza. In Australia, an estimated 100,000 infants are infected by RSV every year. In Victoria, RSV is the most common cause of all reported cases of respiratory tract disease, with an estimated annual cost of $1-4 million. Despite more than 40 years of research there is no vaccine to prevent RSV infection, and the only drug (ribavirin) licenced for treatment of RSV infection is expensive, difficult to administer, toxic, and of doubtful efficacy. We propose to examine one of the RSV proteins, the matrix protein (M). M is very important for virus propagation and is responsible for resultant cell injury. We have observed that M enters the cell nucleus (the location for all cellular DNA and RNA synthesis) where it appears to inhibit host cell RNA synthesis early in infection; later, it exits the nucleus in a step required for virus production in the cytoplasm. The signals that regulate transport of M into and out of the nucleus and the effect on the host cell leading to pathogenesis, are the focus of this proposal. The results of this study will be beneficial in many ways. Most importantly, we will gain knowledge about the processes underlying cell injury caused in RSV disease, which may lead to the identification of novel targets for intervention strategies.Read moreRead less
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.