Determining Regulators Of ILC3 In Mucosal Barrier Function And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$705,209.00
Summary
Innate lymphoid cells (ILCs) are specialized cells that defend the body against invading microorganisms at the body’s surfaces, mediate pathogen clearance and tissue repair but may also drive inflammatory conditions such as allergic asthma and inflammatory bowel disease. We will investigate the molecular switches that regulate this novel cell type and potentially uncover novel molecules or pathways for therapeutic targets.
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.
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 Toxoplasma By The NLRP1 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$623,070.00
Summary
Toxoplasmosa is an endemic pathogen worldwide, approaching 80% of the population in some areas, with a large burden of disease, particularly of immunocompromised and pregnant individuals. Our preliminary data identifies a receptor protein in immune cells that detects Toxoplasma. This can defeat the parasite, but also causes pathology for the host. The outcome of our project will work out what part of Toxoplasma is recognized by this receptor, with significance for the treatment of Toxoplasmosis.
The innate immune response is our primary defence against infection, but must be controlled carefully to avoid chronic inflammation and autoimmunity. Studying tiny regulators of gene function called micro-RNAs and unique cellular pathways, we aim to understand the “big picture” of genetic regulatory systems in innate immunity to provide new insights into inflammation and infection, the genetic basis of diseases, and to identify new potential therapeutic targets, biomarkers and antiviral targets.
My work focuses on cells of the immune system that act as sentinels on the lookout for invading pathogens and danger. These cells are called dendritic cells. I am particularly interested in understanding how these cells function within the bone marrow environment and how they may sense viral infection or cancerous cells within this tissue. We aim to understand their function in specific diseases including Lupus and in pre-leukemia conditions, and also in infectious and parasitic diseases.
Sterile inflammation as a determinant of adaptive immunity. When we injure ourselves, the site of injury becomes inflamed, which may help healing or cause trouble. This project aims to understand how the normal response to injury is controlled and why the process may sometimes go wrong.
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.
Analysing the protective role of platelets during malaria infection. Platelets protect the host during malarial infection. This project aims to study how platelets kill the malaria parasite by investigating the role of host molecules and their potential as novel antimalarial agents. The role of platelets in the pathogenesis of cerebral malaria syndrome will also be investigated.
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.