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
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder. The work has implications for the development of new approaches to prevent and treat UTI.
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.
Molecular Basis Of Asymptomatic Colonization Of The Human Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$461,894.00
Summary
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder and the surface of urinary catheters. The work has implications for the development of new approaches to prevent and treat UTI ....Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder and the surface of urinary catheters. The work has implications for the development of new approaches to prevent and treat UTI.Read moreRead less
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