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Control Of Combined Simian-human Immunodeficiency Virus Infection Utilising NK Cells Mediating Antigen-specific Antibody Dependent Cellular Cytotoxicity - A Novel Vaccine Modality
Funder
National Health and Medical Research Council
Funding Amount
$432,587.00
Summary
Recently, progress was made in developing a vaccine against HIV. Our laboratory was selected to join a global collaboration trying to elucidate the key to this success. Attention has focused on non-neutralizing antibodies and our laboratory has developed a unique expertise in detecting such immune responses. This research will define, purify and manufacture these antibodies and test their ability to prevent HIV in animals with the ultimate aim of producing a vaccine for human use.
Innate Immune Functions Of The Intracellular Antibody Receptor TRIM21
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
The immune system can fight viral infections with antibodies, which mark viruses outside of cells for elimination by immune cells. Antibody-coated viruses try to escape elimination by hiding inside cells. This project will determine how immune cells recognise the antibody-coated viruses ‘hiding’ within them, and the defence response they launch to eliminate viral infection. Such knowledge may allow us to develop better anti-viral drugs and vaccines to fight viral diseases like the common cold.
Dendritic Cells In Innate Immunity And Their Potential Clinical Manipulation
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
Dendritic cells (DC) are rare cells that are crucial in response to infection and surveillance of damaged tissues. We aim to understand the tools that are expressed by DC that allow them to sense pathogens and the functions of different DC types once a pathogen has been detected. The ultimate aim is to be able to understand and harness the functions of different DC so that we may directly target them upon demand to aid in the course of infection or potentially as tumour therapy.
The Role Of A Novel Cytokine Of The Innate Immune Response In Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$344,407.00
Summary
Sexually transmitted infections represent a critical global health and socioeconomic problem with over 1 billion new cases per annum. I propose a world-first description of a new protein that has a protective role against herpes simplex virus (HSV) infection of female reproductive tract. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in HSV-2 infection.
The Identification And Characterisation Of A New DNA Receptor
Funder
National Health and Medical Research Council
Funding Amount
$656,498.00
Summary
The immune system has evolved to fight disease-causing microbes. First, it has to recognize that an infectious agent has invaded. To do this we have developed many probes (receptors) that sense microbial products. Detecting microbial DNA is a critical alarm bell. However, distinguishing pathogen DNA from our own DNA is difficult because both look alike. We have identified a new receptor that helps us identify bacterial DNA and alerts the immune system to the imminent danger.
PB1-F2 Is Critical To Influenza A Virus Pathogenicity Through Activation Of The Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$663,919.00
Summary
Fatal Influenza A virus infections are excessive inflammation. We identified the IAV protein PB1-F2 as critical in driving excessive inflammation via activating the host inflammasome complex. Our study evaluates PB1-F2-mediated inflammation contribution to inflammatory responses. Identifying PB1-F2 in emerging IAV strains is invaluable in aiding health policy makers to quickly assess fatal IAV pandemics. Our research will potentially identify treatment targets towards reducing this inflammation
Production Of Interferon Lambda By Dendritic Cell Subsets And Role In Adjuvant Effects Of Poly I:C
Funder
National Health and Medical Research Council
Funding Amount
$396,541.00
Summary
This proposal describes the identification of specific cells in mouse and humans that produce the anti-viral compound interferon-lambda. We propose to further characterise the mechanisms that induce interferon-lambda expression by these cell types and to decipher how this is controlled at the genetic level. We also aim to determine how the production of interferon lambda by these cell types can influence the immune response to viral infection.
Identification Of Novel Strategies To Mediate Immunity Against Intracellular Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$325,084.00
Summary
The immune system consists of two arms - innate and adaptive. Current vaccine strategies rely mainly on adaptive features of the immune system to mediate immunity against pathogens. Many pathogens have evolved sophisticated strategies to manipulate the adaptive immune system to render it ineffective. This project will investigate microbial detection by the innate immune system, and aims to discover novel, more effective strategies to mediate immunity against intracellular pathogens.
The Role Of Stellate Cells In Fibrosis And Liver Disease Progression In HIV-Hepatitis B Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$157,292.00
Summary
Liver related mortality is the commonest cause of non-AIDS death in HIV infected individuals on treatment. With HIV, HBV liver damage is accelerated and liver-related mortality increased. Understanding how and why is critical to management. I will examine the role of hepatic stellate cells using in vitro models and directly ex vivo from infected patient biopsy tissue. I will investigate the activated of these cells by HIV and HBV infection, thus promoting scar formation with liver injury.
Defining The Interaction Of HIV With The Interferon System In Initial Mucosal Infection
Funder
National Health and Medical Research Council
Funding Amount
$867,716.00
Summary
Very early after virus exposure, immune cells secrete interferons that help limit the spread of viruses within the body. We will investigate the complex interplay between HIV and the interferon system, especially how HIV inhibits the early induction of interferon to aid its spread and then how the body later restores the interferon response. We will also examine how HIV manipulates the interferon system in order to persistent latent reservoirs within tissues.