Asthma and Chronic Obstructive Pulmonary Disease (COPD)
See full list of projectsLUNG DISEASE RESEARCH LABORATORY IN ASTHMA AND COPD
The lung disease research group will be offering projects in the molecular pathogenesis of COPD (chronic obstructive pulmonary disease), a group of diseases that will be the number 3 killer world-wide by 2010 and in severe asthma, a major health problem in Australia in 2007 and lung cancer, now the most common cause of cancer death world-wide.
All of the projects on offer here are based on mouse disease models but form part of larger translation research programs involving patients with lung disease.
Elucidation of signaling pathway involved in IL-11 induced TH2 inflammation in the lung
Supervisor(s): A/Prof M. Ernst and Prof. Gary Anderson
Project Site: Department of Pharmacology, University of Melbourne
Contacts: Prof Gary Anderson T: +61-3-8344-8602 E: gpa@unimelb.edu.au
Project (including aims): Asthma is a debilitating disease that results in extensive matrix remodelling in the lung and immunologically is characterised by the induction of a T cell-driven inflammatory response (Th2 response). This immune response is characterized by the production of factors including the cytokines IL-4 and IL-13. Recent data has shown that the cytokine IL-11, which is produced by a variety of cells in response to inflammatory stimuli, is one of the prime inducers of matrix remodeling and a Th2 response in the lung. Of therapeutic interest is that genetic deletion of the IL-11 receptor as well as inhibition of IL-11 significantly reduced the Th2 response and IL-13 production, and this resulted in a reduction in mucin secretion and inflammatory cells. The project aims therefore to further elucidate mechanisms involved in immune regulation by IL-11 in the lung by using a comprehensive and unique range of existing genetically modified mutant mice, which would be important in developing possible novel avenues of treatment.
Skill Acquisition: In vivo disease models, analysis and genetic complementation of knock-in mouse strains, real-time PCR analysis, histopathological staining of paraformaldehyde and frozen tissue sections, fluorescence activated cell sorting (FACS) analysis, cytokine determination by ELISA, western blotting.
T cell memory in Src mutant mice with viral lung infections
Supervisors: A/Prof Margaret Hibbs (Ludwig Institute), Professor Gary Anderson
Project Site: Department of Pharmacology, University of Melbourne
Contact: Professor Gary Anderson T: 8344 8602 E: gpa@unimelb.edu.au
COPD (chronic obstructive lung disease) patients are particularly susceptible to chest infections, particularly by virus. Respiratory failure after such viral respiratory tract infections is one of the main causes of death of COPD patients but nothing at all is understood as to why they are unusually sensitive to infection. We have created a new genetic model of COPD by mutating kinases that control macrophages and dendritic cells. This project will use this new COPD model and two mouse-adapted lung viruses, RSV and influenza, together with a range of molecular and cell biology methods to identify the inflammatory pathways that re most unregulated in COPD when viruses infect the lungs. A major ficus will be to understand why CD8+ cell anti-viral memory, which should normally protect from infection, does not work efficiently.
Skill acquisition: In vivo disease models, viral culture and characterisation lung function measurement, quantitative PCR, cell and tissue culture, histology, FACS analysis of cell populations; basic T cell immunology, ELISA and Western blotting.
Regulatory T cells and myeloid suppressor cells in asthma and COPD
Supervisors: A/Prof Margaret Hibbs, Dr Steve Bozinovski and Professor Gary Anderson
Project Site: Department of Pharmacology, University of Melbourne
Contact: Professor Gary Anderson T: 8344 8602 E: gpa@unimelb.edu.au
Regulatory T cells (Tregs) are a newly discovered set of cells that limit immune responses in therefore prevent tissue damage. Myloid suppressor cells dampen inflammation but prpmote cancer. There is now a suspicion that Tregs and MSC may be defective in some common inflammatory diseases. In your project you will determine whether Tregs work properly in animal models of asthma and COPD.
Skill acquisition: In vivo disease models, quantitative PCR, cell and tissue culture, histology, FACS analysis of cell populations; immuno-affinity purification of proteins, immune regulation and transduction biochemistry.
Stem cell strategies to cure pulmonary alveolar proteinosis (PAP)
Supervisors: Dr Steve Bozinovski and Professor Gary Anderson
Project Site: Department of Pharmacology, University of Melbourne
Contact: Professor Gary Anderson T: 8344 8602 E: gpa@unimelb.edu.au
Alveolar proteinosis a rare and often fatal disease caused by antibodies against the blood growth factor GM-CSF which arise spontaneous for unknown reasons. In this project you will use a novel stem cell strategy to develop a curative treatment for this orphan disease.
Skill acquisition: In vivo disease models, zymography, quantitative PCR, cell and tissue culture, histology, FACS analysis of cell populations; immuno-affinity purification of proteins, 1D & 2D gels for protein pattern analysis, advanced proteomics (SELDI-ToF, MS/MS), ELISA and Western blotting.
Skeletal muscle failure in COPD
Supervisors: Dr Michelle Hanson and Professor Gary Anderson
Project Site: Department of Pharmacology, University of Melbourne
Contact: Professor Gary Anderson T: 8344 8602 E: gpa@unimelb.edu.au
Patients with COPD often suffer from severe muscle wasting. The cause of this is unknown but wasting is known to increase the risk of death from the disease. Reversing wasting might therefore be a major advance in COPD treatment. In this project you will use advanced gene and protein profiling methods to find new disease pathways that might help stop or reverse wasting. Protein pattern analysis, advanced proteomics (SELDI-ToF, MS/MS). 25.
Inflammation resolving lipids in experimental models of very severe lung inflammation
Supervisors: Professor Gary Anderson, A/Prof Margaret Hibbs, Dr Steve Bozinovski and Professor Bruce Levy, (Harvard Medical School, Boston USA)
Project Site: Department of Pharmacology, University of Melbourne
Contact: Professor Gary Anderson T: 8344 8602 E: gpa@unimelb.edu.au
Inflammation of the lung normally heals completely after injury but in chronic lung disease this does not occur. In this project you will test whether the production and action of newly discovered naturally produced lipids that normally turn off inflammation is defective in chronic inflammatory lung disease.
Skill acquisition: In vivo disease models, zymography, quantitative PCR, cell and tissue culture, histology, FACS analysis of cell populations; immuno-affinity purification of proteins, 1D & 2D gels for protein pattern analysis, advanced proteomics (SELDI-ToF, MS/MS), ELISA and Western blotting.
TH17 cells in lung disease
Supervisors: Professor Gary Anderson and A/Prof Margaret Hibbs
Project Site: Department of Pharmacology, University of Melbourne
Contact: Professor Gary Anderson T: 8344 8602 E: gpa@unimelb.edu.au
IL-17 is a newly discovered cytokine that has rapidly emerged as a major player in lung disease. In this project you will determine why IL-17 is so strongly up-regulated in genetic models of severely lung disease.
Skill acquisition: In vivo disease models, zymography, quantitative PCR, cell and tissue culture, histology, FACS analysis of cell populations; immuno-affinity purification of proteins, 1D & 2D gels for protein pattern analysis, advanced proteomics (SELDI-ToF, MS/MS), ELISA and Western blotting.