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
This application will allow me to restructure my work to provide sufficient time to do full justice to the current and planned commitments of our Respiratory Research Group. Our research programme includes the immunopathology of chronic airway diseases; the epidemiology of respiratory disease (TAHS); clinical physiology technology to service these studies; respiratory clinical pharmacology; microbe-host interactions in CF and COPD; and EBM in chronic respiratory disease self-management .
Investigating The Effects Of Macrolides On Excessive Synthesis And Secretion Of Airway Mucins Using Novel Ex Vivo And In Vivo Approaches
Funder
National Health and Medical Research Council
Funding Amount
$520,821.00
Summary
Many people have difficulty breathing because the airway tubes that move air in and out of their lungs are blocked by excessive amounts of sticky mucus. Our project will use new techniques developed in our laboratories to investigate whether a group of medicines called “macrolides” can prevent the excessive production and release of mucus in the airways, and thus be beneficial in treating asthma, and potentially other lung diseases.
Revolutionising The Diagnosis And Monitoring Of CF Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$818,391.00
Summary
Cystic fibrosis (CF) lung disease starts early in childhood and relentlessly progresses, with early death a common outcome. There is currently no method capable of detecting very early disease onset nor directly assessing the effectiveness of putative treatments. This project will apply our globally unique X-ray imaging tools, which are capable of imaging lung function at any point across the entire lung, for the very early detection of CF and assessment of clinically applicable treatments.
Chronic obstructive pulmonary disease (COPD) causes airway narrowing and lung destruction resulting in breathlessness and cough. Earlier detection of acute attacks of breathlessness may improve treatment, prevent progression and reduce risk of death. The forced oscillation technique can detect attacks earlier and is easy to perform. It will be used in this study for home monitoring with application of time series analyses to accurately detect change so that acute attacks can be treated earlier.
Targeting Remodelling In Chronic Obstructive Pulmonary Disease (COPD), Chronic Asthma And Idiopathic Pulmonary Fibrosis (IPF)
Funder
National Health and Medical Research Council
Funding Amount
$386,634.00
Summary
Lung diseases (emphysema, asthma & pulmonary fibrosis) are major burdens on Australian community and economy. Airway remodelling/wounding is a key feature of all these diseases. Patients experience severe breathlessness seriously impacting quality of life and frequently leading to death. We will assess the potential of new targets (including IL-33), & therapy in suppressing wounding in experimental models. This may lead to a new treatment to reverse or prevent lung diseases.
Mechanisms Of Airway Narrowing In Eosinophilic And Non-eosinophilic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$500,593.00
Summary
Asthma is associated with excessive airway narrowing, increased thickness of the airway wall and inflammation, most typically with eosinophils. However, 50% of cases have few eosinophils and respond less well to current treatments. This project will examine differences in airway structure between patients with or without eosinophils, using post-mortem tissue, as part of an international research collaboration.