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Centre for Cancer Biomarkers CCBIO

CCBIO seminar series

CCBIO Seminar: Herbert Schiller

CCBIO Seminar with speaker Herbert Schiller fra Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Neuherberg, Germany

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Apart from the interesting talks, the CCBIO seminars are a good way to meet CCBIO members and associates. Please feel free to inform others about this seminar as all are welcome both to the lecture and the pizza get-together afterwards.

Invited speakerHerbert Schiller, Comprehensive Pneumology Center, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany
Time: 14:30, Auditorium 4, BBB
Host: Donald Gullberg

Title: "Multi-dimensional proteomics of the extracellular matrix in regeneration and fibrosis"

Abstract

Metazoans evolved ~300 large multidomain extracellular matrix (ECM) proteins, which interact with each other and cells to form elaborate composite biomaterials that shape both the form and function of tissues. The systematic proteomic characterization of ECM niches is still a nascent field of research, which promises to reveal rich information about ECM compositions and protein interaction landscapes of various organ systems in health and disease. In the fibrogenic phase of wound repair, several mesenchymal cell populations secrete and assemble a specialized provisional ECM, which acts as a scaffold and master regulator of developmental programs in concert with extracellular morphogens, such as growth factors, cytokines, and chemokines. Morphogens can interact specifically with ECM proteins and glycosaminoglycans, which alters their biological activity by affecting their signaling capacity, relative positioning to other receptor ligands or their residence time in the tissue. To address this, we developed streamlined proteomic workflows, including a novel quantitative detergent solubility profiling method (QDSP). In QDSP we explored the idea of a quantitative comparison of sequential protein extracts to characterize ECM proteins based on their solubility profiles, which we also used to directly measure the association of secreted proteins with ECM filaments in vivo. The proteome-wide QDSP data served as confirmation of some of the available affinity measurements for ECM interactions and as a starting point for new investigations.

To determine the topology of ECM protein complexes at molecular resolution in their tissue context has not been possible due to technical challenges. The recent successful combination of chemical crosslinking with mass spectrometry (XL-MS), promises to revolutionize structural biology and protein interaction studies. We currently develop ECM protein complex retrieval methods from tissues as well as XL-MS approaches for a ‘discovery mode’ analysis of protein interactions from complex tissue environments in situ. In my presentation I will show examples and discuss ECM proteomics workflows used in our lab.