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.
Dynamics And Mechanisms Of Neutrophil Migration During Tissue Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
Neutrophil granulocytes are central mediators of inflammatory conditions and infections. It is currently unclear how neutrophils navigate through inflamed tissues and how they detect damaged cells and/or pathogens. This proposal will use cutting-edge multi-photon microscopy to dissect the dynamics and mechanisms of neutrophil behaviour in real time in living animals. These experiments will provide a new understanding of the development of inflammatory diseases.
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.
Characterization Of Human-specific Anti-microbial Pathways
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The immune system protects us against infectious disease by killing invading microbes or pathogens. Macrophages are white blood cells that are important for the recognition and destruction of pathogens. This project aims to investigate the role of certain genes, which are turned on in macrophages when they sense invading pathogens, in protecting us against infectious diseases such as tuberculosis and gastroenteritis.
Enhancing Host Defence Against Intracellular Pathogens By Preventing INOS Interaction With A Negative Regulator, SSB-2
Funder
National Health and Medical Research Council
Funding Amount
$448,881.00
Summary
Secretion of nitric oxide (NO) gas by immune cells is a critical defence mechanism for the killing of intracellular pathogens. Production of NO within cells is regulated by the enzyme iNOS. We propose that preventing iNOS from interacting with its natural inhibitor protein (SSB-2) would allow enhanced and prolonged iNOS expression leading to increased NO and increased killing of pathogens such as the mycobacterium tuberculosis and the Leishmania parasite.
Regulation Of Immune And Inflammatory Responses By Short Chain Fatty Acids And GPR43
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
Innate immune mechanisms provide essential signals that determine the outcome of immune responses. The identity of these innate mechanisms may provide opportunities for manipulating immune responses, or controlling inflammatory responses. This proposal centers around a new and little-studied receptor, GPR43, which binds products of bacterial metabolism. This molecular pathway may explain how diet affect immune responses.
New Mechanisms Regulating S100 Protein Function In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$813,929.00
Summary
This project will examine new ways which affect the major effector cells in allergic inflammation and asthma regulated by novel S100 protein mediators. We find a natural protein (S100A12) of the innate immune system, in cells in the lungs of patients with acute asthma. S100A12 activates mast cells to release mediators that trigger asthma attack. We will characterise the proteins with which this protein binds on the cell surface and and determine how this mediates their activation.
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.
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.
The Role Of BAFF, Its Receptor TACI And Toll-like Receptors In Autoimmunity And Tolerance.
Funder
National Health and Medical Research Council
Funding Amount
$486,824.00
Summary
There are 2 types of immune cells, innate cells reacting broadly against microbial elements, and adaptive cells educated to remember pathogens and provide improved immune responses. Most treatments against lupus target the adaptive cells with mixed success. We have discovered a new mechanism driving lupus at the level of innate immunity. This proposal will identify molecular players driving this unappreciated form of lupus and validate new therapeutic targets.