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Systems medicine of chronic inflammatory bowel disease

Objective

Inflammatory bowel disease (IBD) is a major health problem with severe co-morbidities, requiring life-long treatment. Oscillating processes, like biological clocks are well studied and modeled in a number of systems. Circadian rhythms are extremely important for optimal treatments of patients. Recently, the NfkB pathway has been shown to be oscillating. In this project, we will model NfkB oscillation in chronic inflammatory bowel diseases in animal models and patient cohorts with immunosuppressive treatments and controls. The aim is to build an experimentally validated model the NfkB oscillation in 4D within the gut tissue. Dynamic, experimental validation will be done for various types of cells in the gut by a combination of methods, including single-cell based transcriptomics, multi-photon microscopy and time-dependent, multi-component profiling. The validated model framework will enable searching for critical components of the NfB oscillation and to assess their relevance for the disease in patients. Interfering with the oscillation of biological pathways may provide new possibilities to influence biological processes like inflammation. Hence, we will search (assisted by the models and databases developed) for small molecules interfering with the NfkB oscillation in chemical databases and validate selected candidates in experimental systems. To this end, we will use cell lines with the correct indicator constructs using high content microscopy. To better translate the findings in animal models to patients, we will use a mouse model with transplanted human tissue so that we can verify the mathematical model in human tissue and verify functionality of small molecules in vivo.
Owing to its systems, highly focused approach, the project will generate substantial insights into key mechanisms underlying IBD and will provide ways to modulate the oscillatory behavior of the NfB in IBD and IBD-dependent co-morbidities.

Call for proposal

FP7-HEALTH-2012-INNOVATION-1
See other projects for this call

Coordinator

THE UNIVERSITY OF MANCHESTER
Address
Oxford Road
M13 9PL Manchester
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 3 262 748
Administrative Contact
Claire Faichnie (Mrs.)

Participants (12)

CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL
Germany
EU contribution
€ 1 493 400
Address
Olshausenstrasse 40
24118 Kiel
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Susanne Neufeldt (Ms.)
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany
EU contribution
€ 849 997
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Activity type
Research Organisations
Administrative Contact
Ina Krischek (Dr.)
THE UNIVERSITY OF WARWICK
United Kingdom
EU contribution
€ 942 410
Address
Kirby Corner Road - University House
CV4 8UW Coventry
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Peter Hedges (Dr.)
UNIVERSITAETSKLINIKUM AACHEN
Germany
EU contribution
€ 994 800
Address
Pauwelsstrasse 30
52074 Aachen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Volker Legewie (Mr.)
THE UNIVERSITY OF LIVERPOOL
United Kingdom
EU contribution
€ 992 250
Address
Brownlow Hill 765 Foundation Building
L69 7ZX Liverpool
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jenny Lawson (Ms.)
UNIVERSITEIT MAASTRICHT
Netherlands
EU contribution
€ 1 095 434
Address
Minderbroedersberg 4
6200 MD Maastricht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Joseh I.H. Janssen (Dr.)
THE HEBREW UNIVERSITY OF JERUSALEM
Israel
EU contribution
€ 849 999
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jane Turner (Ms.)
LIFEGLIMMER GMBH
Germany
EU contribution
€ 600 000
Address
Markelstrasse 38
12163 Berlin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Susanne Hollmann (Dr.)
GENEXPLAIN GMBH
Germany
EU contribution
€ 499 960
Address
Am Exer 19 B
38302 Wolfenbuttel
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Holger Michael (Dr.)
THE UNIVERSITY OF AUCKLAND
New Zealand
EU contribution
€ 18 000
Address
Princes Street 24
1010 Auckland
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Julia Zhu (Mrs.)
GABO:MI GESELLSCHAFT FUR ABLAUFORGANISATION:MILLIARIUM MBH & CO KG

Participation ended

Germany
EU contribution
€ 219 940
Address
Oskar Von Miller Ring 29
80333 Muenchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Birgit Fuchs (Mrs.)
ARTTIC
France
EU contribution
€ 181 060
Address
Rue Du Dessous Des Berges 58A
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Martin Dietz (Dr.)