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
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.
Protease Activated Receptor 2 Antagonist In Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,347.00
Summary
The immune response to infection involves a network of proteins that produce an inflammatory response. Sometimes this response is prolonged or uncontrolled and can lead to a large number of inflammatory and other diseases. We have discovered a class of drugs that can bind to a particular protein on the surface of human cells and control this inflammatory response. This property has the potential to treat a wide range of inflammatory and other diseases in humans.
The Neural Control Of Serotonin Release From Intestinal Enterochromaffin (EC) Cells
Funder
National Health and Medical Research Council
Funding Amount
$117,187.00
Summary
Many functional gastrointestinal problems are believed to be caused by a disruption of the normal functioning of the nerves within the wall of the gut. These nerves are believed to receive information about the contents of the intestine from a specialised class of cell lining the inside wall of the gut called the enterochromaffin cell. The enterochromaffin cell does this job by modulating the release of the transmitter serotonin. In some disorders, like the Irritable Bowel Syndrome (IBS) which c ....Many functional gastrointestinal problems are believed to be caused by a disruption of the normal functioning of the nerves within the wall of the gut. These nerves are believed to receive information about the contents of the intestine from a specialised class of cell lining the inside wall of the gut called the enterochromaffin cell. The enterochromaffin cell does this job by modulating the release of the transmitter serotonin. In some disorders, like the Irritable Bowel Syndrome (IBS) which can affect the upper and lower intestine, the information that serotonin carries can become confused. Thus, the control of the release of serotonin from the enteroendocrine cell is an important process to understand in health and in disease. We will investigate this release directly in isolated tissues from guinea pig small and large intestine and from human large intestine. This study will examine the role of serotonin and the modulation of its release from the enterochromaffin cell. Problems with serotonin release may underlie disease, thus, understanding how this release is controlled will provide a foundation for new and specific therapies that target channels or receptors specific to the release of serotonin. These data could help to develop therapies for gastrointestinal problems such as the IBS, chronic intestinal pseudo-obstruction and gastro-oesophageal reflux disease. The release of serotonin is also intimately linked with the diarrhea associated with cholera and anti-cancer treatments. The proposed study will contribute to the ongoing development of specific therapies that block serotonin receptors on the nerve terminal and will lead to new therapies that compliment existing therapies by modulating the release of serotonin.Read moreRead less
Unraveling IL-1F7: A Neglected IL-1 Family Member With Big-Stage Potential
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
Cytokines are messenger proteins used by most cells of the body. Since their role as master regulators of many biological processes was discovered, cytokines have enjoyed the limelight of biomedical research. Anti-inflammatory cytokines are particularly coveted as they could replace side effect-prone anti-inflammatory drugs like aspirin. We identified an anti-inflammatory cytokine (IL-1F7) and revealed its protective activity in common, severe diseases like myocardial infarction. We will now exp ....Cytokines are messenger proteins used by most cells of the body. Since their role as master regulators of many biological processes was discovered, cytokines have enjoyed the limelight of biomedical research. Anti-inflammatory cytokines are particularly coveted as they could replace side effect-prone anti-inflammatory drugs like aspirin. We identified an anti-inflammatory cytokine (IL-1F7) and revealed its protective activity in common, severe diseases like myocardial infarction. We will now explore how IL-1F7 exerts is protective properties.Read moreRead less
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
Neuroimmune Interactions In Functional And Organic Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are chronic, incurable diseases of the lower gastrointestinal tract with unknown causes and poor treatment options. Both the immune and nervous systems are altered in GI disease, but have traditionally been studied in isolation. My research investigates how the neuro-immune axis is altered in these diseases, using animal models and human tissue samples to identify novel treatment options for these debilitating diseases.
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.
Vagal Nerve Stimulation As A Novel Therapy In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,502.00
Summary
Inflammatory bowel disease (IBD) is common exerting a large personal and societal burden to the Australian population. Current medications used to treat IBD are expensive, have many side effects and at times require hospitalisation for their administration. We aim to develop the non invasive and inexpensive technique of vagal nerve stimulation as a novel treatment strategy for IBD.