Lung infections are the most frequent triggers of asthma exacerbations. While different infections cause exacerbations by they all result in the same type of lung inflammation. Using novel disease models, we have identified key molecules involved in a range of viral and bacterial induced asthma exacerbations. We will define these shared pathways that link viral and bacterial-mediated asthma exacerbations, thus these studies will pave the way for the development of unified treatments.
Defining The In Vivo Contribution Of Leukocyte Extracellular Traps To Infective Disease
Funder
National Health and Medical Research Council
Funding Amount
$598,363.00
Summary
Neutrophils are the white blood cells that protect against infection. A surprising protective neutrophil behaviour was recently described – neutrophils can pack up their internal DNA and antimicrobial enzymes and explosively release them into their surrounds, forming a “Neutrophil Extracellular Trap” (NET). This project uses zebrafish built have fluorescent neutrophils to study NET release in living animals. We will learn how NETs control infection and what goes wrong when NETs cause disease.
The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.
Understanding The Role Of MAIT Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,593.00
Summary
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells protect us from bacteria and yeast at mucosal sites where the body's immune defences are most easily breached, e.g. gut, oral cavity, airways & reproductive tract. This study investigates the role of MAIT cells in health and in diseases like inflammatory bowel disease, peptic ulceration, periodontitis and tuberculosis. Controlling MAIT cells could help in treating these conditions.
Therapeutic Vaccine Against Non-Hodgkin's Lymphoma Targeting The Immune Adjuvant Properties Of Natural Killer T Cells.
Funder
National Health and Medical Research Council
Funding Amount
$451,606.00
Summary
Patients with lymphoma cancers initially respond well to treatment, but later relapse with disease. The immune system can be effective at controlling cancer. A potential treatment option is to boost the natural immune response against cancer. This study investigates a vaccine that activates a certain immune cell, NKT cells, to fight lymphomas by delivering an NKT cell-activating molecule. Outcomes will allow assessment of combining an NKT-based vaccine with established treatments for lymphoma.
Using Influenza Vaccination To Understand And Improve Anti-viral Immunity In COPD
Funder
National Health and Medical Research Council
Funding Amount
$1,316,597.00
Summary
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. Lung infections often make those afflicted by COPD very unwell. We have recently shown that influenza vaccination induces a poor antibody response in many COPD patients. This study will examine why this is the case, and what can be done to restore normal immune function. In the final year of the Project, we will assess whether doubling the dose of influenza vaccination is helpful.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
Investigating Mechanisms Of Axonal Pathology Following Oligodendrocyte Apoptosis: Avenues For Neuroprotection In Early MS
Funder
National Health and Medical Research Council
Funding Amount
$678,138.00
Summary
Recent research suggests that Multiple Sclerosis could first be triggered by the death of a type of brain cell called an oligodendrocyte. These cells insulate nerve cells in the brain which help them function normally. We will test the idea that death of oligodendrocytes impairs nerve cell function by causing inflammation and by depriving nerve cells of energy. We will determine whether preventing inflammation and feeding the nerve cells an alternative source of energy can restore normal functio ....Recent research suggests that Multiple Sclerosis could first be triggered by the death of a type of brain cell called an oligodendrocyte. These cells insulate nerve cells in the brain which help them function normally. We will test the idea that death of oligodendrocytes impairs nerve cell function by causing inflammation and by depriving nerve cells of energy. We will determine whether preventing inflammation and feeding the nerve cells an alternative source of energy can restore normal function.Read moreRead less
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
The Impact Of The Neonatal Gut Microbiome On Specific And Nonspecific Vaccine Responses.
Funder
National Health and Medical Research Council
Funding Amount
$661,496.00
Summary
Humans are colonised by a large and diverse group of microorganisms, collectively known as the microbiome. The gut microbiome, in particular, hosts an enormous abundance and diversity of bacteria, which perform a range of essential beneficial functions. Our study will investigate whether disruption of the gut microbiome in newborns, for example through antibiotic usage or maternal diet, leads to an impairment of subsequent immune responses to childhood immunisations.