Cytoplasmic DNA As A Danger Signal For Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
DNA in mammalian cells is contained within a structure known as the nucleus. The presence of DNA outside the nucleus in the cytoplasm of the cell is a sure sign that something is wrong, and may indicate the presence of a viral invader. In this case, the cell initiates anti-viral responses, including production of anti-viral proteins and death of the infected cell to stop replication of the virus. Lack of proper control of these responses may contibute to the autoimmune disease lupus.
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.
Where It All Begins- Exploring Dendritic Cell Control Of Viral Infection And Cell Development In The Bone Marrow Of Mice And Man.
Funder
National Health and Medical Research Council
Funding Amount
$96,335.00
Summary
The bone marrow (bm) is the birthplace of all blood cells that fight infection in the body. Dendritic cells (DC), essential for starting immune responses, are found in the bm but the exact types and their functions are unknown. I plan to investigate the DC types that reside in the bm and explore their role in inducing immune responses and in influencing the development of cells from the bm with potential attributable benefits for stem cell transplant and vaccine design.
Inflammasome Function In Protection Against Infectious Disease And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Inflammation, characterised by swelling, heat, pain and redness, is a normal response to injury and infection. Many human diseases such as gout, athersclerosis, diabetes and Alzheimer’s disease involve some inflammation, mediated through a common pathway termed the inflammasome. This project will investigate the proteins involved in this pathway and how they interact in their normal role of combatting infections, as well as a possible defect in this pathway in autoimmune patients.
Argonaute Proteins In The Mammalian Antiviral Response
Funder
National Health and Medical Research Council
Summary
Viruses are the most abundant infectious agents on earth, and the diseases caused by them are a constant threat and cause of mortality worldwide. Awarded the Nobel Prize for Medicine in 2006, RNA interference (RNAi) is a natural process that plants use to attack viruses. Humans possess all of the tools for RNAi, but whether it is used for antiviral defense is unknown. This study aims to uncover this immune process which will open new avenues to treat virus infections, such as influenza and HIV.
Inhibition Of Necroptosis As A Novel Strategy For The Prevention Of Bronchiolitis And Subsequent Asthma
Funder
National Health and Medical Research Council
Funding Amount
$658,015.00
Summary
Severe virus associated bronchiolitis is a major cause of infant mortality and a risk factor for asthma. Using a mouse model, we have shown that virus infection causes tissue damage, leading to the release of 'danger' molecules that promote excessive inflammation and tissue remodelling. We have identified an important mechanism by which the danger molecules are released. We will now assess whether blocking this process ameliorates viral bronchiolitis and breaks its nexus with subsequent asthma.
Understanding The Host Pathogen Relationships Of Hendra Virus In Bats, Horses And Humans
Funder
National Health and Medical Research Council
Funding Amount
$648,339.00
Summary
We will examine why bats can be infected with Hendra Virus with no apparent symptoms, yet the virus causes severe disease in other mammals including humans. We will examine the innate immune response towards the virus in the natural host (fruit bats), horses and humans. In addition to the innate immune response we will also examine the adaptive immune response in bats and humans. We hope this information can be used to design new drugs or vaccines to Hendra Virus.
Unconventional Mechanisms For Activating The NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$747,031.00
Summary
Many inflammatory driven diseases such as arthritis, atherosclerosis and septic shock are also associated with cell death. This project will identify, at the molecular level, how cell death signalling specifically acts to trigger pathological inflammation. As such, it will identify novel targets for the development of next generation anti-inflammatory drugs.
The Inflammasome In Host Defence And Autoinflammation
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Inflammation is one of the bodies first responses to infection. The inflammasome is a protein complex that activates pro-inflammatory cytokines as part of this process. We are investigating pathogens that activate a specific inflammasome complex, and also an inflammatory disease it may cause when activated accidentally, in the absence of infection. We are also investigating pathways that keep this inflammation in check, and how pathogens might hijack these anti-inflammatory pathways to promote i ....Inflammation is one of the bodies first responses to infection. The inflammasome is a protein complex that activates pro-inflammatory cytokines as part of this process. We are investigating pathogens that activate a specific inflammasome complex, and also an inflammatory disease it may cause when activated accidentally, in the absence of infection. We are also investigating pathways that keep this inflammation in check, and how pathogens might hijack these anti-inflammatory pathways to promote infection.Read moreRead less
A Study Of The Function Of Neuronal Apoptosis Inhibitory Proteins (NAIP) In Innate Immunity.
Funder
National Health and Medical Research Council
Funding Amount
$242,696.00
Summary
The innate immune system is the first line of defence against infection and cancer. Regulation of the immune system is extremely important as too little response can lead to severe infections, whilst too much response can lead to chronic inflammatory disease. This project will examine the role of �neuronal apoptosis inhibitory protein� in the immune system, which should provide information on regulation of innate immunity, as well as provide insight to neurodegenerative diseases and cancer.