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IMMUNOBIOME SIGNED

Identifying microbiotal triggers of inflammatory bowel disease through the lens of the immune system

Total Cost €

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EC-Contrib. €

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Partnership

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 IMMUNOBIOME project word cloud

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

throughput    microbial    resolve    perpetuators    core    hypomorphic    disruptive    health    first    underpinning    harnessing    interface    effect    overlapping    search    inappropriate    characterises    revealed    mice    manifest    vigorous    rising    microbiota    methodologically    infectious    healthy    immunoglobulins    complexed    diseases    entirely    potentially    strategy    points    miip    world    overcome    limitations    prevalence    igg    risk    mucosal    uncover    orthologues    associations    identification    metagenomic    structural    inflammatory    hence    unravel    ibd    pathological    dysbiosis    patients    prevails    massive    ulcerative    triggers    disease    seq    handling    builds    tier    harbouring    impossible    bowel    humanised    lens    exemplified    alterations    genes    crohn    genetic    host    relationships    impaired    active    immune    debilitating    genetically    microbes    colitis    immunologically    sequencing    intestinal    exceeding    prediction    dominant    iga    hierarchy    termed    individuals    environmental    induction    incidence    transfer    directed    aberrant    immunoprecipitation    leprosy   

Project "IMMUNOBIOME" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

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 United Kingdom [UK]
 Project website http://www.med.cam.ac.uk/kaser/research/
 Total cost 2˙304˙375 €
 EC max contribution 2˙304˙375 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 2˙304˙375.00

Map

 Project objective

The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis manifest at the host-microbiota interface. The recently revealed genetic underpinning of IBD points towards an aberrant immune response to the intestinal microbiota. The prediction of genetically-impaired microbial handling is exemplified by key risk genes overlapping between leprosy, an infectious disease, and Crohn’s disease. A vigorous search for microbial triggers of IBD, which could also help explain the rising incidence and prevalence of this debilitating condition throughout the world, via high-throughput sequencing studies have indeed revealed structural alterations of the microbiota (‘dysbiosis’) compared to healthy individuals, although it is methodologically impossible to resolve cause-effect relationships of these associations. Here we propose a two-tier strategy to overcome these limitations of current methods to uncover the microbial targets of the ‘inappropriate’ immune response that characterises IBD. The first tier is based on an entirely novel, and potentially disruptive, method (termed MiIP-Seq - Microbial Immunoprecipitation and Sequencing) that we have developed. MiIP-Seq allows directed metagenomic sequencing of microbes complexed with immunoglobulins in patients with IBD, and hence the identification of those microbes within the microbiota that are targeted by the pathological IgG immune response; induction of massive mucosal IgG exceeding IgA that prevails in health is a core characteristic of IBD. The second tier builds on transfer of the microbiota from patients with active IBD harbouring dominant IBD risk genes into mice genetically hypomorphic at the orthologues of these risk genes, and to resolve the hierarchy of immunologically targeted microbes within the humanised microbiota via MiIP-Seq. Hence, via exploiting the lens of the immune system and harnessing genetic insight, this study will unravel the ‘environmental, microbial’ triggers and perpetuators of IBD.

 Publications

year authors and title journal last update
List of publications.
2019 Joep Grootjans, Niklas Krupka, Shuhei Hosomi, Juan D. Matute, Thomas Hanley, Svetlana Saveljeva, Thomas Gensollen, Jarom Heijmans, Hai Li, Julien P. Limenitakis, Stephanie C. Ganal-Vonarburg, Shengbao Suo, Adrienne M. Luoma, Yosuke Shimodaira, Jinzhi Duan, David Q. Shih, Margaret E. Conner, Jonathan N. Glickman, Gwenny M. Fuhler, Noah W. Palm, Marcel R. de Zoete, C. Janneke van der Woude, Guo-Cheng Yuan, Kai W. Wucherpfennig, Stephan R. Targan, Philip Rosenstiel, Richard A. Flavell, Kathy D. McCoy, Andrew J. Macpherson, Arthur Kaser, Richard S. Blumberg
Epithelial endoplasmic reticulum stress orchestrates a protective IgA response
published pages: 993-998, ISSN: 0036-8075, DOI: 10.1126/science.aat7186
Science 363/6430 2020-01-15
2019 Georg Schneditz, Joshua E. Elias, Ester Pagano, M. Zaeem Cader, Svetlana Saveljeva, Kathleen Long, Subhankar Mukhopadhyay, Maryam Arasteh, Trevor D. Lawley, Gordon Dougan, Andrew Bassett, Tom H. Karlsen, Arthur Kaser, Nicole C. Kaneider
GPR35 promotes glycolysis, proliferation, and oncogenic signaling by engaging with the sodium potassium pump
published pages: eaau9048, ISSN: 1937-9145, DOI: 10.1126/scisignal.aau9048
Science Signaling 12/562 2020-01-15
2018 Nicole C. Kaneider, Arthur Kaser
Personalized Treatment in Inflammatory Bowel Disease: For Another Time
published pages: , ISSN: 0016-5085, DOI: 10.1053/j.gastro.2018.09.004
Gastroenterology 2020-01-15
2016 Joep Grootjans, Arthur Kaser, Randal J. Kaufman, Richard S. Blumberg
The unfolded protein response in immunity and inflammation
published pages: 469-484, ISSN: 1474-1733, DOI: 10.1038/nri.2016.62
Nature Reviews Immunology 16/8 2020-01-15
2018 Shuhei Hosomi, Joep Grootjans, Yu-Hwa Huang, Arthur Kaser, Richard S. Blumberg
New Insights Into the Regulation of Natural-Killer Group 2 Member D (NKG2D) and NKG2D-Ligands: Endoplasmic Reticulum Stress and CEA-Related Cell Adhesion Molecule 1
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.01324
Frontiers in Immunology 9 2020-01-15
2018 Konrad Aden, Florian Tran, Go Ito, Raheleh Sheibani-Tezerji, Simone Lipinski, Jan W. Kuiper, Markus Tschurtschenthaler, Svetlana Saveljeva, Joya Bhattacharyya, Robert Häsler, Kareen Bartsch, Anne Luzius, Marlene Jentzsch, Maren Falk-Paulsen, Stephanie T. Stengel, Lina Welz, Robin Schwarzer, Björn Rabe, Winfried Barchet, Stefan Krautwald, Gunther Hartmann, Manolis Pasparakis, Richard S. Blumberg, Stefan Schreiber, Arthur Kaser, Philip Rosenstiel
ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS–STING
published pages: jem.20171029, ISSN: 0022-1007, DOI: 10.1084/jem.20171029
The Journal of Experimental Medicine 2020-01-15
2016 Konrad Aden, Ateequr Rehman, Maren Falk-Paulsen, Thomas Secher, Jan Kuiper, Florian Tran, Steffen Pfeuffer, Raheleh Sheibani-Tezerji, Alexandra Breuer, Anne Luzius, Marlene Jentzsch, Robert Häsler, Susanne Billmann-Born, Olga Will, Simone Lipinski, Richa Bharti, Timon Adolph, Juan L. Iovanna, Sarah L. Kempster, Richard S. Blumberg, Stefan Schreiber, Burkhard Becher, Mathias Chamaillard, Arthur Kaser, Philip Rosenstiel
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation
published pages: 2208-2218, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.07.054
Cell Reports 16/8 2020-01-15
2017 Shuhei Hosomi, Joep Grootjans, Markus Tschurtschenthaler, Niklas Krupka, Juan D. Matute, Magdalena B. Flak, Eduardo Martinez-Naves, Manuel Gomez del Moral, Jonathan N. Glickman, Mizuki Ohira, Lewis L. Lanier, Arthur Kaser, Richard Blumberg
Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation
published pages: 2985-2997, ISSN: 0022-1007, DOI: 10.1084/jem.20162041
The Journal of Experimental Medicine 214/10 2020-01-15
2017 Arthur Kaser, Richard S. Blumberg
The road to Crohn\'s disease
published pages: 976-977, ISSN: 0036-8075, DOI: 10.1126/science.aao4158
Science 357/6355 2020-01-15
2017 Markus Tschurtschenthaler, Timon E. Adolph, Jonathan W. Ashcroft, Lukas Niederreiter, Richa Bharti, Svetlana Saveljeva, Joya Bhattacharyya, Magdalena B. Flak, David Q. Shih, Gwenny M. Fuhler, Miles Parkes, Kenji Kohno, Takao Iwawaki, C. Janneke van der Woude, Heather P. Harding, Andrew M. Smith, Maikel P. Peppelenbosch, Stephan R. Targan, David Ron, Philip Rosenstiel, Richard S. Blumberg, Arthur Kaser
Defective ATG16L1-mediated removal of IRE1α drives Crohn’s disease–like ileitis
published pages: 401-422, ISSN: 0022-1007, DOI: 10.1084/jem.20160791
The Journal of Experimental Medicine 214/2 2020-01-15

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