Viral Infection And TGFbeta Impair Glucocorticoid Activity In Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$617,699.00
Summary
Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, espe ....Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, especially those affecting the lung.Read moreRead less
Viral Infection And Transforming Growth Factor-beta Impair Glucocorticoid Activity In Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$318,299.00
Summary
Anti-inflammatory types of steroid drugs are commonly used in chronic lung disease including asthma and chronic obstructive pulmonary disease. However, a significant number of sufferers show resistance to the steroid therapy. Our study is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are identifying novel therapeutic targets to improve the effectiveness of treatment of chronic disease.
Airway Smooth Muscle And Fixed Airway Obstruction: Strategies For Softening Muscle
Funder
National Health and Medical Research Council
Funding Amount
$555,643.00
Summary
In severe asthma the airways don't relax fully making breathing more difficult. The inability to relax is being addressed by exploring the behaviour of isolated muscle cells. These cells are able to compact collagen gels. The mechanisms used to compact the gel are different to those that cause rapid muscular contraction. We aim to identify the molecules responsible for the gel compaction as a first step to identifying new drugs to treat the fixed airway obstruction in severe asthma.
Targeting Small Airways To Overcome Resistance To Therapy In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$531,045.00
Summary
There is a pressing need to overcome resistance to current therapies for severe asthma. Targetting inflammation-induced changes in small airway contraction offers an alternative strategy. We have identified a novel bronchodilator that relaxes maximally contracted mouse small airways when current treatment is ineffective. We will demonstrate its efficacy in animal models mimicking key features of human asthma, and define new ways to improve outcomes in poorly-controlled asthma.
Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches ....Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches off inflammation. Essential knowledge into why this receptor pathway fails to switch off inflammation will be determined. Furthermore, the development of targeting strategies to this receptor represents an innovative approach to blocking damaging and chronic airway inflammation.Read moreRead less
Understanding the biology of reactive oxygen species. This project will utilise forefront technologies to identify and characterise fundamental biological processes involving toxic free radicals that cause infectious disease and cancer. The approach synergises with researchers across disciplines and universities to ultimately identify future drugs to improve and maintain health.
Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on rec ....Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.Read moreRead less
Glucocorticoid Resistance: Identifying New Anti-inflammatory Drug Targets
Funder
National Health and Medical Research Council
Funding Amount
$453,287.00
Summary
The control of chronic inflammatory diseases such as asthma involve use of drugs related to the steroid hormone cortisol. Up to 40% of patients with more severe disease respond poorly or not at all to these drugs. The remaining non-steroid treatments are only partially effective. Poor disease control is a great health and economic burden. We have identified a molecular mechanism for steroid resistance and propose new studies to identify novel drugs that act to reverse steroid resistance.
Pontine control of adaptive breathing behaviour in health and disease. This project will develop an understanding of the fundamental brain mechanisms associated with adaptive breathing during behaviour such as speech or swallowing. Adaptive breathing is impaired in lung disease, dementia and autism. This project will provide new insight to global brain function and treatment of central respiratory disorder.