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.
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
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.
A Prospective, Randomised, Double-blind Trial Of Extended- Versus Bolus-infusion ?-lactam Therapy In Infective Exacerbations Of Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$148,431.00
Summary
I am an infectious diseases physician focused on the most effective way to use antibiotics to treat infections. People with cystic fibrosis often get lung infections and the bacteria that causes this, Pseudomonas aeruginosa, can be difficult to treat. I will be investigating whether infusing antibiotics over a prolonged period of time is more effective than standard therapy in treatment of Pseudomonas aeruginosa lung infections in patients with cystic fibrosis.
A Phase 1b Trial Of Specific Immunotherapy For Recurrent Respiratory Papillomatosis
Funder
National Health and Medical Research Council
Funding Amount
$141,208.00
Summary
This project will determine whether immunisation can be used to effectively treat an existing infection. To date, immunisation has only been used to prevent infection, but there are many chronic infections where intervention might help the body's defences to to a better job and clear the chronic infection. In this study, we will work out whether this approach can be applied to a virus infection ( papillomavirus) which is associated with cancer. We will test immunisation against a chronic and lif ....This project will determine whether immunisation can be used to effectively treat an existing infection. To date, immunisation has only been used to prevent infection, but there are many chronic infections where intervention might help the body's defences to to a better job and clear the chronic infection. In this study, we will work out whether this approach can be applied to a virus infection ( papillomavirus) which is associated with cancer. We will test immunisation against a chronic and lifethreatening disorder in which warts grow in the respirarory tract, as there is currently no satisfactory treatment for this. If the project is successful we may also learn which blood tests are likely to predict the outcome of immunisation to treat infection.Read moreRead less
Establishing The Capacity For H5N1 Challenge Of Ferrets Within Australia &optimizing Pandemic Vaccines In This Model
Funder
National Health and Medical Research Council
Funding Amount
$405,513.00
Summary
Australia is currently in the process of manufacturing vaccines for use in people against strains of avian influenza viruses circulating in South East Asia as part of a national preparedness program for an influenza pandemic. These particular avian flu viruses are capable of causing severe disease and death in humans as well as birds, although at present they are not highly transmissible between people. Should the avian influenza viruses mutate to gain this capability, it will be necessary to in ....Australia is currently in the process of manufacturing vaccines for use in people against strains of avian influenza viruses circulating in South East Asia as part of a national preparedness program for an influenza pandemic. These particular avian flu viruses are capable of causing severe disease and death in humans as well as birds, although at present they are not highly transmissible between people. Should the avian influenza viruses mutate to gain this capability, it will be necessary to institute widespread vaccination of the Australian population. It is not possible to test the vaccines in people for their effectiveness against avian influenza infection prior to a disease outbreak, so an animal model for the disease will be used to assist in optimizing the formulation of flu vaccines and in testing their efficacy in preventing infection or reducing the severity of disease. Ferrets are natural hosts for flu viruses, have similar responses to vaccination as people, and develop a similar disease to humans when infected with influenza. These animals will be used to assist vaccine manufacturers in providing the best type of vaccine for protection of Australians in the face of a global flu pandemic.Read moreRead less
Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not ju ....Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not just in Australia, but globally to inform pandemic planning and disease control policy around emerging infections and bioterrorism.Read moreRead less