Roles And Regulation Of Sphingosine Kinase 1 During Dengue Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$482,795.00
Summary
Dengue virus (DENV) infection is a global human disease with an estimated 50 million infections annually and there is no vaccine or therapy. DENV disease is worsended by the way the body responds to infection and we have investigated these responses. We know the virus changes a molecule in the body called sphingosine-kinase 1 (SK1), which normally controls if cell live or die and how they function. This study will characterise how DENV influences SK1 and if we can target this interaction to deve ....Dengue virus (DENV) infection is a global human disease with an estimated 50 million infections annually and there is no vaccine or therapy. DENV disease is worsended by the way the body responds to infection and we have investigated these responses. We know the virus changes a molecule in the body called sphingosine-kinase 1 (SK1), which normally controls if cell live or die and how they function. This study will characterise how DENV influences SK1 and if we can target this interaction to develop new drugs against DENV infection.Read moreRead less
Characterize The Post-entry Events Of HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
For HIV to successful infect a target cell, it must properly remove the outer layers of its protective gears (outer viral protein coats) to allow the viral genetic materials to be replicate (duplicate and multiplied) for the generation of their ‘offspring viruses’. This process is known as viral uncoating, and it is arguably one of the least understood areas of HIV. In this proposal, we will use a number of complementary state-of-the-arts research tools to characterize the HIV uncoating process.
Current anti-HIV therapies can't cure HIV because HIV remains silent(latent) in long-lived cells. The HIV life cycle and virus production is linked to activation of the host cell, which is regulated by dendritic cells. This grant will explore how the factors controlling T cell activation and proliferation control virus expression and latency. By understanding how latent infection is established and maintained, these studies will potentially identify new ways to eliminate HIV infection.
Targeting Myeloid Cells To Restrict Gamma-herpesvirus Spread
Funder
National Health and Medical Research Council
Funding Amount
$643,152.00
Summary
Gamma-herpesviruses infect most people and cause cancers. Vaccines to date have worked poorly. We have identified a key role for myeloid cells in infection that suggests a new approach. Interferons restrict infection in some myeloid cells. We will test whether inducing interferons can make all myeloid cells restrictive and reduce chronic infection. We will test then whether myeloid-restricting antibodies can recruit the same defences to provide a basis for vaccination.
Understanding The Role Of Host Arih2 In Defence Against Viral Infection And Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,737.00
Summary
A set of proteins, called E3 ligases, modulate many aspects of immunity. Arih 2 is a novel E3 ligase that limits immune cell activation to maintain the immune system in a quiescent state. The details of how Arih2 functions and its role in immunity to chronic overwhelming infection are the focus of this study. The insights gained from these studies have important implications for our understanding of how immune responses can be promoted during infection or halted in autoimmunity.
Real Time Visualisation Of T Cell Cycling During Influenza Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$589,679.00
Summary
Influenza remains a major health threat, particularly in the elderly population. Here we will unravel the mechanisms underlying the expansion of killer T cells, a crucial part of the anti-influenza immune response. Using intravital multi-photon microscopy, we will follow the cell cycle dynamics of individual T cells in real time during different stages of influenza. We will further elucidate how ageing impacts on T cell proliferation. Together, this will provide insight into the mechanisms of an ....Influenza remains a major health threat, particularly in the elderly population. Here we will unravel the mechanisms underlying the expansion of killer T cells, a crucial part of the anti-influenza immune response. Using intravital multi-photon microscopy, we will follow the cell cycle dynamics of individual T cells in real time during different stages of influenza. We will further elucidate how ageing impacts on T cell proliferation. Together, this will provide insight into the mechanisms of anti-viral immunity and immuno-senescence.Read moreRead less
Mapping The Steps And Deciphering The Mechanisms Crucial In Dendritic Cell Development.
Funder
National Health and Medical Research Council
Funding Amount
$582,064.00
Summary
Dendritic cells (DCs) are a type of white blood that kick-start immune responses. There are various types of DCs that specialize in, for example, clearing viral, bacterial or fungal infections, and are even used to fight cancer. Understanding how DCs grow, therefore, has many clinical benefits. This project aims to understand these processes and identify new regulators of their growth using cutting edge technologies and strategies.
Immunoregulation And Adoptive Immunotherapy Of Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$391,784.00
Summary
This project is investigating link between a common herpesvirus and brain cancer. We are also aiming to develop new killer T cell-based therapy to target herpesvirus proteins in cancer cells with a long-term objective to use this information to develop a therpeutic vaccine against brain cancer.
Following The T Cell Repertoire Over The Human Life Course
Funder
National Health and Medical Research Council
Funding Amount
$473,159.00
Summary
T cells are critical to human health being our second and last line against infectious disease and cancer. However, we know very little about how this important immune compartment operates on a top-down scale. This project will use new technology to resolve this immune compartment to high detail. We will then use this new method to track the T cell compartment from the first years of life and across years of adult life to see how this vital immune compartment evolves along the human life course.
Determinants Of CTL Recruitment Into The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$474,647.00
Summary
The size of CD8+ T cell (CTL) responses is central to their efficacy in virus control, and can be substantially influenced by how effectively they are recruited and expand after infection. This study will determine the impact of both CTL characteristics and antigen abundance on CTL recruitment and expansion after infection. Understanding the nature of these influences will enable a more informed approach to the clinical manipulation of CTL responses.