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.
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
Structural And Functional Characterisation Of The Killer Cell Immunoglobulin-like Receptor (KIR) Family Of Natural Killer Cell Receptors
Funder
National Health and Medical Research Council
Funding Amount
$348,070.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used to guide in the selection of bone marrow donors in the treatment of leukemias as well as understanding how we fight off infections.
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
Mammals have evolved an array of mechanisms to sense microbes. These immune sentinels must distinguish self from non-self to activate an immune response. The initiation, amplification and quenching of an immune response is carefully orchestrated to eliminate invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that prevent inflammatory diseases such as cardiovascular disease, hepatitis, inflammatory bowel disease and skin diseases.
Characterization Of Novel, Colitis Associated Pathobionts To Identify Therapeutic Targets In The Host Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$684,609.00
Summary
Applying cutting edge methods to grow bacteria from the human gut, we have identified three species, two previously unknown, that are found in many inflammatory diseases including Inflammatory bowel disease, colorectal cancer and in cancer immunotherapy patients who experience colitis. By characterizing these bacteria and the immune response in human cells we are seeking to discover novel targetted methods to prevent colitis and gastrointestinal inflammation.
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.
A Systems-biology Approach To Understanding The Beneficial Heterologous Effects Of Neonatal BCG Vaccination In A Melbourne-based Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$846,853.00
Summary
BCG vaccine (usually used to protect against TB) also enhances the immune system of young babies to protect them against infections other than TB. We have a large collection of blood samples from a study in which babies were randomised to be given BCG vaccine at birth or no BCG. We will use these to understand the immunological and molecular mechanisms by which BCG boosts the immune system to protect against infections other than TB.
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.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes and Alzheimer’s. This project will reveal how the body produces interleukin-1? – a protein at the heart of inflammation and disease – so we can design better strategies for treating patients with inflammation-driven disease.