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Understanding The Interplay Between ER Stress And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$560,918.00
Summary
Chronic inflammatory diseases in the gut and lung affect hundreds of thousands of Australians. We have identified how inflammation causes a type of stress resulting in abnormal protein synthesis in the cells which make the barrier to microbes. Following an infection this process might be the trigger for chronic unresolving inflammatory disease. The further understanding of this process we seek in this project is likely to lead new approaches to treat common inflammatory diseases.
Muc1 Regulation Of The NLRP3 Inflammasome In The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
The mucin Muc1 is an important part of the barrier against infection in the gut, and appears to protect against development of bacterial inflammatory disease. We have identified that Muc1 suppresses activation of the inflammasome (a mechanism by which pathogens cause inflammation). We will now examine how Muc1 does this and explore the importance of this effect on inflammatory disease in the intestine. This may identify novel approaches for protecting against gastric and colorectal cancer.
Pathogenesis Of A New Mouse Model Of Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$682,820.00
Summary
Ankylosing spondylitis and Crohn's disease are autoimmune inflammatory diseases which cause long-term pain and deformity of joints, spine and bowel. Using a new mouse model of both diseases, we will study cells and processes involved in the initiation of disease, in order to discover new targets for prevention and treatment. The work will have importance for design of new therapies for human inflammatory spine and bowel diseases.
Regulation Of NOD Signalling By IAPs And RIP Kinases
Funder
National Health and Medical Research Council
Funding Amount
$643,172.00
Summary
Alterations in NOD signalling have been implicated in various human inflammatory diseases, particularly in Crohn’s disease and asthma. In this project we will identify new molecules that regulate NOD signalling and test the effect of drugs that inhibit known components of these pathways to determine their utility in treating inflammatory diseases.
Cell Surface Mucins In Gastrointestinal Infection, Inflammation And Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$469,627.00
Summary
Cell surface mucins are protective molecules that line all the wet surface of the body, including the gastrointestinal tract. Our research has uncovered that mucins regulate cell growth and cell death. Inappropriate control by the mucins, could lead to chronic inflammation and formation of cancers. We will test how important these molecules are in the development of cancers in the intestine, and further explore the mechanism of action.
Estimation And Partitioning Of The Still-missing Heritability For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$291,856.00
Summary
We have pioneered the use of multi-marker statistical genetic methods in human genetics to elucidate the genetic architecture of complex traits, including common diseases. We have shown that between a third and a half of additive genetic variation is captured by common genetic variants, leaving two-thirds to a half truly ‘missing’. In this proposal we will test our hypothesis that the still-missing heritability is due to low frequency causal variants. Applications of genomic medicine require thi ....We have pioneered the use of multi-marker statistical genetic methods in human genetics to elucidate the genetic architecture of complex traits, including common diseases. We have shown that between a third and a half of additive genetic variation is captured by common genetic variants, leaving two-thirds to a half truly ‘missing’. In this proposal we will test our hypothesis that the still-missing heritability is due to low frequency causal variants. Applications of genomic medicine require this fundamental knowledge to progress fully.Read moreRead less
We use a mouse model of inflammatory bowel disease (IBD) to determine how sensations from the inflamed gut are processed in the spinal cord. Over 60,000 Australians suffer from IBD and debilitating pain is a major symptom. Surprisingly, we know very little about how pain signals originating in the normal or the diseased gut are organised and processed in the central nervous system. Obtaining such information is a necessary first step before we can develop therapies to relieve gut pain.
A Novel Nanoparticulate Iron Supplement And Its Effect On The Gastrointestinal Tract.
Funder
National Health and Medical Research Council
Funding Amount
$671,995.00
Summary
Iron deficiency and iron deficiency anaemia are major global health issues. Currently available iron supplements can lead to gastrointestinal side effects. We have developed a new type of oral iron supplement that (in animal studies) is as effective as conventional treatments, but without their limitations. In this project we will investigate the effect of this supplement on the gastrointestinal tract to ensure its safety and to provide preliminary data for future clinical trials in humans.
Host Cell Death Signaling And Susceptibility To Bacterial Gut Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,321.00
Summary
Bacterial infections are a major cause of infectious disease worldwide. Here we aim to characterise immune responses that help fight infection by E. coli and Salmonella. These bacteria have evolved ways to shut down many of our immune responses during infection, allowing them to survive and cause disease. This work will help understand the complex relationship between gut bacteria and our immune system and provide solutions for controlling infection and treating immune disorders of the gut.
Epithelial Metabolism As A Mediator Of Host-microbiome Interactions In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$833,648.00
Summary
This project examines how the changes in the intestinal environment during inflammation influences the behaviour of bacteria within the micobiome and whether those changes can be counteracted to sustain a healthy microbiome, even during episodes of disease. This work uses cell and animal models to examine how inflammation changes the intestinal nutrients that the microbiome requires to maintain its community and whether supplementing the microbiome with these nutrients can prevent disease.