I am a physician-scientist whose research involves the role of monocyte-macrophages in HIV pathogenesis and low cost methods for monitoring HIV infection in resource-constrained countries
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.
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.
HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional thro ....HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional throughout adult life. The role of the thymus in HIV-1 infection remains controversial. Studies of the role of the thymus in HIV-1-infected individuals has been limited by the lack of a marker of thymic function in vivo. We have recently developed a novel assay to quantify cells of recent thymic origin by taking advantage of certain molecular events that occur in the thymus during the production of new T lymphocytes. This molecular event creates a circular piece of DNA, called a T-cell receptor excision circles (TREC). TREC concentration in the periphery will increase with an increase in thymic output but will reduce in the presence of T cell proliferation or cell death. In order to determine the contribution of the thymus to immune reconstitution following HAART, we plan to study the dynamics of thymus function in HIV-1 infection by measuring TREC and T cell turnover in HIV-1 infection prior to and following HAART. In a subgroup of individuals, more commonly seen following treatment of HIV-1 infection in children, there is an increase in CD4+ T lymphocytes in the absence of a significant reduction in viral suppression. The role of the thymus in this unique subset of individuals will be studied.Read moreRead less
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
Application Of Mathematical Modelling And Development Of Decision Support Tools For Mosquito-borne Disease
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Mosquito-borne disease affects millions of people in Australia and overseas. Reducing the prevalence of these diseases requires an understanding of their transmission, drug resistance and role of external factors such as climate. This project will use newly developed mathematical and statistical tools to investigate transmission of malaria, and improve the reporting of Ross River and Barmah Forest viruses and dengue. Project outcomes will assist the development of evidence based policy.
Processes Underlying Establishment And Maintenance Of The Latent HIV Resevoir And Potential Impact Of Integrase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$318,044.00
Summary
Therapy for HIV-infected individuals is currently able to control the growth of the virus, but cannot eradicate the viral infection. This is due to a pool of CD4+ T lymphocytes which contain HIV DNA in a latent state, ready to reactivate as soon as therapy is interrupted. This project aims to better understand how this pool of latently infected CD4+ T lymphocytes is established and maintained, particularly how it is linked to the essential T cell survival signal from interleukin 7.
There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this proj ....There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this project is to investigate the liver disease caused by HBV in co-infected patients and the development of antiviral resistance due to the long-term treatment with lamivudine. We will develop a data base to monitor virological, biochemical and histological parameters for each of these co-infected patients. We will collate all information on these patients that are attending these various centres. This data base will be essential for monitoring the disease in patients with a poor immune system versus patients with a normal immune system. The HBV virus isolated from these patients will be characterised by sequence analysis. The sequence analysis of these viruses will be compared before and after treatment to determine any resistance markers that have developed. These resistant markers will be copied into an infectious clone using specialised molecular techniques. Clones containing these resistant markers will be analysed in the laboratory to determine the antiviral sensitivity to lamivudine and a number of new drugs against hepatitis B virus. This information will be important in treating patients that are co-infected with HBV and HIV and have already developed resistance to lamivudine.Read moreRead less