Systems Biology of the Extracellular Niche in Chronic Lung Disease
| Dates: | 22 June 2015 |
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| Times: | 12:00 - 13:00 |
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| What is it: | Academic calendar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Herbert Schiller |
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This is a FLS Special Seminar.
Abstract: Despite the tremendous interest in ECM biology in the context of regenerative medicine and cancer research, the proteomic characterization of extracellular matrix niches is a much underexplored area of research. We develop advanced mass spectrometry workflows to study cellular and extracellular composition of tissues and the signalling landscape of cellular mechanosensing (shotgun proteomics), as well as the architecture of ECM structures (crosslinking mass spectrometry), and currently apply them to the process of fibrosis and regeneration in the lung.
In the first part of my seminar, I will give an overview of the range of mass spec workflows we are using and possible future developments and research directions. In the second part of my seminar I will highlight our recent study on lung injury and repair, which was just accepted for publication in EMBO Molecular Systems Biology.
In this study, we monitored remodeling of the extracellular niche in tissue repair in the bleomycin-induced lung injury mouse model. Mass spectrometry quantified 8366 proteins from total tissue and bronchoalveolar lavage fluid over the course of eight weeks, surveying tissue composition from the onset of inflammation and fibrosis to its full recovery. Combined analysis of proteome, secretome and transcriptome highlighted post-transcriptional events during tissue fibrogenesis and defined the composition of airway epithelial lining fluid. To comprehensively characterize the ECM, we developed a quantitative detergent solubility profiling method (QDSP), which identified Emilin-2 and Collagen-XXVIII as novel constituents of the provisional repair matrix. QDSP revealed which secreted proteins interact with the ECM, and showed drastically altered association of morphogens to the insoluble matrix upon injury. Thus, our proteomic systems biology study assigned proteins to tissue compartments and uncovered their dynamic regulation upon lung injury and repair, potentially contributing to the development of anti-fibrotic strategies.
Speaker
Herbert Schiller
Organisation: Max Planck Institute of Biochemistry, Martinsried
Travel and Contact Information
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Lecture Theatre
Michael Smith Building
Manchester
