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MUC2GO SIGNED

THE ROLE OF MUCINS AND MUCUS IN THE DISEASES CYSTIC FIBROSIS, CELIAC DISEASE, AND ULCERATIVE COLITIS

Total Cost €

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EC-Contrib. €

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Partnership

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 MUC2GO project word cloud

Explore the words cloud of the MUC2GO project. It provides you a very rough idea of what is the project "MUC2GO" about.

luminal    defense    bacteria    previously    fundamental    diseases    poorly    epithelial    layer    host    special    glycosylated    tract    impenetrable    intestine    capacity    reveal    innate    celiac    unresolved    line    human    intestinal    separating    colon    basic    hypothetic    strands    crypts    separate    medical    muc2    molecules    sensory    international    lung    cell    bacterial    transfer    proteins    treatments    discovered    ulcerative    signaling    act    dependent    world    pave    initiator    western    function    seems    structure    mucin    protection    edge    trapped    formed    instrumental    glands    layers    disease    mucosal    surfaces    colitis    cystic    protect    normal    inner    epithelium    place    chronic    goblet    mucus    cells    dynamic    immune    smaller    mechanisms    skeleton    cleared    suggest    first    substantially    respiratory    tracheal    mucins    fibrosis    trachea    mouse    molecular    protecting    accumulation    area    gliadin    fragments    attached    transgenic    position    fluorescent    single   

Project "MUC2GO" data sheet

The following table provides information about the project.

Coordinator
GOETEBORGS UNIVERSITET 

Organization address
address: VASAPARKEN
city: GOETEBORG
postcode: 405 30
website: www.gu.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Project website http://www.medkem.gu.se/mucinbiology
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    GOETEBORGS UNIVERSITET SE (GOETEBORG) coordinator 2˙500˙000.00

Map

 Project objective

The overall aim of this proposal is to explain how the mucus systems of the intestine and lung act as a first innate immune defense line to protect our mucosal surfaces. Mucins are of highly glycosylated proteins that build the mucus skeleton. We previously discovered that there are two mucus layers in the colon. The inner mucus layer built around the MUC2 mucin is attached and impenetrable to bacteria, thus separating the intestinal bacteria from the epithelial cells. However, how the dynamic colon mucus layers are formed and controlled is poorly understood. We have established an international leading position in this research area and will now address fundamental and unresolved problems of high medical importance. The capacity of the inner mucus layer to separate bacteria from the epithelium is highly dependent on the luminal bacteria. Our results suggest specific bacteria signaling via smaller molecules or bacterial fragments to the host to increase protection. We will reveal how this signaling take place, important for understanding increased western world diseases including ulcerative colitis. Of special interest is our recent finding of a single sensory goblet cell protecting the colon crypts. We have developed a fluorescent human MUC2 transgenic mouse that is instrumental for the planned studies as well as in studies of gliadin uptake from the intestine and initiator for celiac disease. We will now transfer our leading edge knowledge of intestinal mucus structure and function to the respiratory tract. Normal trachea seems to be cleared by mucus strands formed the tracheal glands, but these strands are trapped cystic fibrosis. We will also reveal how a hypothetic attached mucus layer, as described by us in colon, could explain the mucus accumulation in chronic lung diseases. The proposed project will substantially increase our basic understanding of molecular mechanisms behind several mucus related diseases and pave the way for new treatments.

 Publications

year authors and title journal last update
List of publications.
2020 Liisa Arike, Andrus Seiman, Sjoerd van der Post, Ana M. Rodriguez Piñeiro, Anna Ermund, André Schütte, Fredrik Bäckhed, Malin E.V. Johansson, Gunnar C. Hansson
Protein Turnover in Epithelial Cells and Mucus along the Gastrointestinal Tract Is Coordinated by the Spatial Location and Microbiota
published pages: 1077-1087.e3, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.12.068
Cell Reports 30/4 2020-03-05
2019 Joana K. Volk, Elisabeth E.L. Nyström, Sjoerd van der Post, Beatriz M. Abad, Bjoern O. Schroeder, Åsa Johansson, Frida Svensson, Sofia Jäverfelt, Malin E.V. Johansson, Gunnar C. Hansson, George M.H. Birchenough
The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function
published pages: jem.20190679, ISSN: 0022-1007, DOI: 10.1084/jem.20190679
The Journal of Experimental Medicine 2019-10-03
2019 Eran Blacher, Stavros Bashiardes, Hagit Shapiro, Daphna Rothschild, Uria Mor, Mally Dori-Bachash, Christian Kleimeyer, Claudia Moresi, Yotam Harnik, Maya Zur, Michal Zabari, Rotem Ben-Zeev Brik, Denise Kviatcovsky, Niv Zmora, Yotam Cohen, Noam Bar, Izhak Levi, Nira Amar, Tevie Mehlman, Alexander Brandis, Inbal Biton, Yael Kuperman, Michael Tsoory, Leenor Alfahel, Alon Harmelin, Michal Schwartz, Ad
Potential roles of gut microbiome and metabolites in modulating ALS in mice
published pages: 474-480, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1443-5
Nature 572/7770 2019-10-03
2019 Génesis Vega, Anita Guequén, Malin E. V. Johansson, Liisa Arike, Beatriz Martínez-Abad, Elisabeth E. L. Nyström, Paolo Scudieri, Nicoletta Pedemonte, Pamela Millar-Büchner, Amber R. Philp, Luis J. Galietta, Gunnar C. Hansson, Carlos A. Flores
Normal Calcium-Activated Anion Secretion in a Mouse Selectively Lacking TMEM16A in Intestinal Epithelium
published pages: , ISSN: 1664-042X, DOI: 10.3389/fphys.2019.00694
Frontiers in Physiology 10 2019-10-03
2019 Markus Furter, Mikael E. Sellin, Gunnar C. Hansson, Wolf-Dietrich Hardt
Mucus Architecture and Near-Surface Swimming Affect Distinct Salmonella Typhimurium Infection Patterns along the Murine Intestinal Tract
published pages: 2665-2678.e3, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.04.106
Cell Reports 27/9 2019-10-03
2019 Hannah Schneider, Evelin Berger, Brendan Dolan, Beatriz Martinez-Abad, Liisa Arike, Thaher Pelaseyed, Gunnar C. Hansson
The human transmembrane mucin MUC17 responds to TNFα by increased presentation at the plasma membrane
published pages: 2281-2295, ISSN: 0264-6021, DOI: 10.1042/bcj20190180
Biochemical Journal 476/16 2019-10-03
2017 Rielana Wichert, Anna Ermund, Stefanie Schmidt, Matthias Schweinlin, Miroslaw Ksiazek,Philipp Arnold,Katharina Knittler,Frederike Wilkens,1 Barbara Potempa, Bjorn Rabe, Marit Stirnberg, Ralph Lucius,Jorg W. Bartsch,Susanna Nikolaus, Maren Falk-Paulsen, Philip Rosenstiel, Marco Metzger, Stefan Rose-John,Jan Potempa, Gunnar C. Hansson, Peter J. Dempsey,and Christoph Becker-Pauly
\"Mucus Detachment by Host Metalloprotease Meprin β Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB\"
published pages: 2090-2103, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.10.087
CELL Reports 21 2019-06-13
2018 Bjoern O. Schroeder, George M.H. Birchenough, Marcus Ståhlman, Liisa Arike, Malin E.V. Johansson, Gunnar C. Hansson, Fredrik Bäckhed
Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration
published pages: 27-40.e7, ISSN: 1931-3128, DOI: 10.1016/j.chom.2017.11.004
Cell Host & Microbe 23/1 2019-06-13

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