Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
Modelling The Effects Of Immunity On Influenza Transmission - Implications For Prevention And Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$275,767.00
Summary
There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our proj ....There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our project will use data from historic and contemporary outbreaks of influenza and build mathematical models to explain the rate of growth of an influenza outbreak in terms of: 1. The proportion of people exposed to influenza who do not become ill (although there can be evidence of infection if careful studies are made). This proportion is about 33%. 2. The proportion of people who are protected from influenza by immunity, whether induced by vaccination or by past exposure to natural influenza infection (this can vary from 0% in isolated populations which have not seen influenza for many years up to 80 or 90% in urbanised populations that are exposed to influenza almost every season). 3. Different rates of contact between different people and groups of people - some may be exposed so often that their immunity is boosted regularly without them becoming severely ill; others, living in more isolated circumstances, may be rarely exposed, but when they are, they are more likely to become severely ill. 4. The effects of influenza vaccine in inducing protective immunity - it is well known that there is good protection if the vaccine is well matched to the circulating virus. 5. The effects of live virus infection in inducing (short-lived) protection against a wider range of influenza viruses. Our model results will be used to guide vaccine design and pandemic planning.Read moreRead less
Unravelling The Mechanism Of MHC Class-I Associated Drug Hypersensitivities
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Some drugs cause adverse reactions that are life threatening. We think these reactions are mediated by killer T cells as they are genetically controlled by immune response genes that normally guide immunity to microbes. We will study immune reactions to the drug abacavir, used to treat HIV (AIDS); allopurinol used to prevent gout and carbamazepine, used to treat epilepsy. The study may also help devise better treatments for patients who experience severe forms of these reactions.
The Role Of Renal Dendritic Cells In Infection And Immunity Under Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$475,143.00
Summary
Kidney transplantation is the best treatment for kidney failure but it is frequently complicated by bacterial and viral infections that can cause rejection and may cause loss of the kidney. This grant will study the role that dendritic cells in the kidney play in causing rejection and preventing infection. With the knowledge gained from these studies, we will be able to discover new ways to prevent rejection and treat infections of the kidney post transplant.
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less