Cell Surface Mucins In Gastrointestinal Mucosal Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
Summary
Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe t ....Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe that these molecules trigger epithelial cell defensive responses to the presence of microorganisms. The proposed research aims to prove these propositions and to elucidate the molecular mechanisms underlying function of cell surface mucins. Understanding the function of cell surface mucins could lead to the development of new drugs to treat epithelial inflammation such as that seen in inflammatory bowel diseases and respiratory diseases such as asthma and cystic fibrosis.Read moreRead less
Prof McGuckin is studying common chronic diseases (gut and respiratory inflammatory diseases, arthritis, and obesity and diabetes) that are major contributors to poor health in the Australian community and are major contributors to healthcare expenditure. His research includes basic studies elucidating the biological basis of these diseases and then uses this new knowledge to develop new therapeutic approaches to treatment. The new therapeutic approaches will be tested in model systems as a prel ....Prof McGuckin is studying common chronic diseases (gut and respiratory inflammatory diseases, arthritis, and obesity and diabetes) that are major contributors to poor health in the Australian community and are major contributors to healthcare expenditure. His research includes basic studies elucidating the biological basis of these diseases and then uses this new knowledge to develop new therapeutic approaches to treatment. The new therapeutic approaches will be tested in model systems as a prelude to clinical trials.Read moreRead less
Towards Selective Targeting Of HDACs For Anti-inflammatory Applications
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
HDAC inhibitors are anti-cancer drugs that kill rapidly growing cells (like cancer cells). These drugs also have anti-inflammatory properties and so may be beneficial in chronic inflammatory diseases such as as Rheumatoid Arthritis. However, it is unknown how they reduce inflammation. In this project we aim to understand how HDAC inhibitors act as anti-inflammatory agents and to design new HDAC inhibitors with reduced side effects for the treatment of inflammatory diseases.
The Role Of The Intestinal Epithelium In Gliadin Peptide Influx In Coeliac Disease
Funder
National Health and Medical Research Council
Funding Amount
$503,566.00
Summary
Food products made from cereals such as wheat are part of the staple diet for much of the world but unfortunately they trigger coeliac disease in 1:100 individuals including more than 100,000 Australians. This project aims to determine where the disease inducing proteins cross the cells that line the intestine to enter the body. It also aims at increasing the health of these cells to produce a barrier that can prevent the disease inducing proteins from entering the body.
Activated Platelets As Unique Targets For Early Imaging And Site-directed Therapy Of Cardiovascular And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$846,979.00
Summary
Heart attack and inflammatory diseases such as rheumatoid arthritis und multiple sclerosis either kill or severely disable people. We use the presence of platelets early on in these diseases to develop methods for early diagnosis as well as potential drugs for site-directed therapy. We have developed new biotechnological tools to perform novel high sensitivity imaging in Positron Emission Tomography (PET) and laser light imaging as well as a localised anti-inflammatory therapy.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes, Alzheimer’s and Parkinson's. This research program will reveal how the body deactivates inflammasomes – protein complexes at the heart of inflammation and disease – so we can design better drugs for treating patients with inflammation-driven disease.
Many white blood cells have an innate ability to sense infection, and trigger inflammation to fight invading microbes. These innate immune cells use particular receptors to sense pathogens and we have now identified a new pathway that leads to the activation of one of these, known as Pyrin. Genetic mutations can activate this pathway, and our project will determine the molecular basis for this, and how it can be targeted to treat inflammatory disease.
Recycling Endosomes Governing Cell Polarity And Cytokine Secretion.
Funder
National Health and Medical Research Council
Funding Amount
$958,412.00
Summary
Cytokines are chemical messengers released by cells to mount inflammatory responses to fight infections. The timing and direction of cytokine release must be tightly regulated. We investigate the cellular compartments and molecules that control cytokine secretion using sophisticated live cell imaging. Uncontrolled cytokine release is the main cause of ongoing inflammation in arthritis and inflammatory bowel disease and our studies aim to identify cellular targets for new drug development.
Regulation Of Cytokine Signalling: Structure And Biophysical Characterisation Of Key Protiens
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
Cells are informed when to grow, divide, migrate or die by protein molecules called cytokines. The cellular response to cytokines needs to be carefully regulated or else inflammation and other disorders will result. The SOCS (Suppressors Of Cytokine Signalling) family of proteins are a major regulator of cytokine signalling. This work will examine the structure and interactions of this important protein class.
Inflammation is essential to help fight infection and repair tissues. However when overactive it causes diseases such as psoriasis, arthritis and inflammatory bowel disease. Less well known, inflammation also helps drive development of cancers. My research aims to understand inflammatory signalling at the molecular and organism level. Experience has shown that this knowledge can be translated to improve existing therapies or generate new ones, and that is the ultimate aim of my research.