COPD and Asthma
See full list of projectsLung Disease Research Laboratory in COPD and asthma
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.
Src kinases, lung inflammation and lung cancer
Supervisors: A/Prof Margaret Hibbs (Ludwig Institute) and Professor Gary Anderson (Department of Pharmacology, University of Melbourne)
Contact details: Tel: 8344 8602, 9341 3155; Email: gpa@unimelb.edu.au; Margaret.Hibbs@ludwig.edu.au
Lung cancer is now the most common cause of cancer death in the world. We have discovered that mutations in Src kinases cause lung cancer even though the mutated kinases are not themselves expressed in lung tissue. Deregulated inflammation seems to be the underlying problem. This project will study exactly how inflammation causes lung cancer.
Skill acquisition: In vivo disease models, quantitative PCR, cell culture, histology, FACS analysis of cell populations; immuno-affinity purification of proteins, immune regulation and transduction biochemistry.
Genetic and pharmacologic approaches to dissect lung inflammation and lung cancer
Supervisors: A/Prof Margaret Hibbs (Ludwig Institute) and Professor Gary Anderson (Department of Pharmacology, University of Melbourne)
Contact details: Tel: 8344 8602, 9341 3155; Email: gpa@unimelb.edu.au; Margaret.Hibbs@ludwig.edu.au
Chronic obstructive pulmonary disease (COPD) is an incurable and often fatal inflammatory lung disease, and is a known risk factor for lung cancer. We have a number of animal models of inflammatory lung disease, including mice with activating mutations in Src family kinases, and mice with deleterious mutations in the inositol phosphatase SHIP-1 or the protein tyrosine phosphatase SHP-1. The aim of this project is to use genetic approaches to identify genes that predispose to inflammatory lung disease, and pharmacologic methods to reverse establish disease.
Skill acquisition: In vivo disease models, quantitative PCR, cell culture, histology, FACS analysis of cell populations; immuno-affinity purification of proteins, immune regulation and transduction biochemistry.
Elucidation of signaling pathway involved in IL-11 induced TH2 inflammation in the lung
Supervisor(s): Dr. Andrew Jarnicki and Prof. Gary Anderson
Location: Department of Pharmacology, University of Melbourne
Contact Details: (AJ) Tel: +61-3-9341-3148 Email: jarnicki@ludwig.edu.au
(GA) Tel: +61-3-8344-8602 Email: gpa@unimelb.edu.au
Project (including aims): Asthma is a debilitating disease that results in extensive matrix remodeling 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 (Department of Pharmacology, University of Melbourne)
Contact details: Tel: 8344 8602, 9341 3155; Email: gpa@unimelb.edu.au; Margaret.Hibbs@ludwig.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 are most deregulated in COPD when viruses infect the lungs. A major focus 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, lung function measurement, quantitative PCR, cell culture, histology, FACS analysis of cell populations; basic T cell immunology, ELISA and Western blotting.
Regulatory T cells in Asthma and COPD
Supervisors: A/Prof Margaret Hibbs (Ludwig Institute) and Professor Gary Anderson (Department of Pharmacology, University of Melbourne)
Contact details: Tel: 8344 8602, 9341 3155; Email: gpa@unimelb.edu.au; Margaret.Hibbs@ludwig.edu.au
Regulatory T cells (Tregs) are a newly discovered set of cells that limit immune responses and therefore prevent tissue damage. There is now a suspicion that Tregs 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 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
Location: Department of Pharmacology, University of Melbourne
Contact details: 8344 8602 Email: 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
Location: Department of Pharmacology, University of Melbourne
Contact details: 8344 8602 Email: 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.
Identification of Lyn regulated proteins using proteomics
Supervisor: A/Prof Margaret Hibbs (Ludwig Institute)
Contact details: Tel: 9341-3155; Email: Margaret.Hibbs@ludwig.edu.au
The Lyn protein tyrosine kinase plays an essential role in the immune system and is critical for a wide variety of processes including B cell development, dendritic cell maturation and function, mast cell responses, and macrophage developmental programming and activation. Using standard biochemical approaches, we have identified some substrates of the Lyn kinase; these proteins are modified post-transcriptionally, and this process is dependent on the presence or absence of an active Lyn kinase. The aim of this project is to identify additional Lyn-regulated genes in macrophages derived from Lyn mutant mice using proteomics technology. The proposed experiments are aimed at identifying important novel proteins that are critical regulators of macrophage development, activation and innate immune responses.
Skill acquisition: Cell culture, histology, Western blotting, immuno-affinity purification of proteins, 1D & 2D gels for protein pattern analysis, advanced proteomics (SELDI-ToF, MS/MS).
Inflammation resolving lipids in experimental models of very severe lung inflammation
Supervisors: Professor Gary Anderson, A/Prof Margaret Hibbs and Professor Bruce Levy, (Harvard Medical School, Boston USA)
Location: Department of Pharmacology, University of Melbourne
Contact details: Tel: +61 3 8344 8602 Email: 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
Location: Department of Pharmacology, University of Melbourne
Contact details: Tel: +61 3 8344 8602 Email: 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.
LUNG STEM CELL BIOLOGY/BERTONCELLO LAB
The broad interest of the Lung Stem Cell Biology Laboratory is to characterise epithelial and mesenchymal stem cells in the normal and diseases lung, including chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and cancer. Our long-term goal is to investigate the role of stem cells in lung homeostatis, and identify factors regulating their regenerative potential as a prerequisite to the development of therapeutic strategies to attenuate lung disease and regenerate the injured lung.
Our group is a member of the Adult Stem Cell Program funded by the Australian Stem Cell Centre Collaborative Stream Initiative which comprises a national network of high calibre scientists with internationally recognised leadership in adult stem cell biology focused on working collaboratively to address key areas that will allow significant acceleration of stem cell research.
The laboratory performs cutting edge research using flow cytometry-based cell separative strategies, novel three-dimensional cell culture assays and in vivo transplantation to identify and characterise stem/progenitor cells in the adult lung. Current projects offered in the laboratory aim to elucidate the mechanisms by which epithelial and mesenchymal stem/progenitor cells contribute to homeostasis in the lung and how they are regulated by the microenvironmental niche in which they reside.
Defining the lineage specificity of adult lung epithelial stem/progenitor cells
Supervisor(s): Dr Jonathan McQualter, Professor Gary Anderson, A/Professor Ivan Bertoncello
Location: Department of Pharmacology, University of Melbourne
Contact Details: A/Prof Ivan Bertoncello Email: Ivan.Bertoncello@stemcellcentre.edu.au,
Professor Gary Anderson T: +61-3-8344-8602 Email: gpa@unimelb.edu.au
We have developed a novel 3D culture assay based on the epithelial-mesenchymal-matrix intereactions in the lung which enables the identification of lung epithelial stem/progenitor cells by their colony-forming potential in vitro. We have identified a population of epithelial stem/progenitor cells which generate colonies comprising airway, alveolar, or mixed lung epithelial cell lineages in vitro, suggesting for the first time that an epithelial stem/progenitor cell hierarchy exists in the adult lung. This project will advance on these cell culture techniques to identify the cues that regulate the survival, self-renewal and lineage specificity of different stem/progenitor celll subsets.
Supervisor(s): Dr Jonathan McQualter, Professor Gary Anderson, A/Professor Ivan Bertoncello
Location: Department of Pharmacology, University of Melbourne
Contact Details: A/Prof Ivan Bertoncello Email: Ivan.Bertoncello@stemcellcentre.edu.au,
Professor Gary Anderson T: +61-3-8344-8602 Email: gpa@unimelb.edu.au
This project will analyse the temporal pattern of depletion and recovery of lung epithelial stem/progenitor cells following lung injury by exploiting the selective toxicity of drugs which impair lung function. Cell culture analysis of the proliferation, self-renwal and lineage specificity of lung eppithelial stem/progenitor cells at various stages of injury and repair will rpovide valuable insights into the role of endogenous epithelial stem cells in regneration and repair of the adult lung.
The role of lung stromal cells in the regulation of lung epithelial stem cell proliferation and differentiation
Supervisor(s): A/Professor Ivan Bertoncello, Professor Gary Anderson, Dr Rosa McCarty
Location: Department of Pharmacology, University of Melbourne
Contact Details: A/Prof Ivan Bertoncello Email: Ivan.Bertoncello@stemcellcentre.edu.au,
Professor Gary Anderson T: +61-3-8344-8602 Email: gpa@unimelb.edu.au
This project will analyse the different lung stromal cell populations which comprise lung epithelial stem cell lniches and compare their ability to regulate lung epithelial stem/progenitor cell proliferation and differentiation. Cell culture assays will be used to determine how lung stromal cells alone, or togethr with growth factors and matrix proteins affect the lung epithelial regeneration.