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.
Specialised immune cells, called cytotoxic T cells, circulate through the body, and kill infected cells to protect us from disease. We discovered that a protein, DOCK8, is important for the regulation of T cell function. Importantly, humans with mutations in the DOCK8 gene suffer from a debilitating, and potentially lethal, immunodeficiency disease. This project will therefore elucidate the role of DOCK8 in immune cells, to better understand the consequences of DOCK8 deficiency for immunity.
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.
LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.
Modulating Cellular Copper Levels To Prevent The Effects Of Excitotoxicity In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
Exitotoxicity has been implicated in many neurological disorders incluing Alzheimer's and Huntington's disesaes. This toxicity can be inhibited by modulated intracellular copper levels. Here we will ascertain the therapeutic potential of strategies designed to increase cellular copper levels.
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.