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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.
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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)

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CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL

Germany

EU Contribution

€ 1 493 400

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

Germany

EU Contribution

€ 849 997

THE UNIVERSITY OF WARWICK

United Kingdom

EU Contribution

€ 942 410

UNIVERSITAETSKLINIKUM AACHEN

Germany

EU Contribution

€ 994 800

THE UNIVERSITY OF LIVERPOOL

United Kingdom

EU Contribution

€ 992 250

UNIVERSITEIT MAASTRICHT

Netherlands

EU Contribution

€ 1 095 434

THE HEBREW UNIVERSITY OF JERUSALEM

Israel

EU Contribution

€ 849 999

LIFEGLIMMER GMBH

Germany

EU Contribution

€ 600 000

GENEXPLAIN GMBH

Germany

EU Contribution

€ 499 960

THE UNIVERSITY OF AUCKLAND

New Zealand

EU Contribution

€ 18 000

GABO:MI GESELLSCHAFT FUR ABLAUFORGANISATION:MILLIARIUM MBH & CO KG

Germany

EU Contribution

€ 219 940

ARTTIC

France

EU Contribution

€ 181 060

Project information

Grant agreement ID: 305564

Status

Closed project

  • Start date

    1 December 2012

  • End date

    30 November 2017

Funded under:

FP7-HEALTH

  • Overall budget:

    € 15 784 306,68

  • EU contribution

    € 11 999 998

Coordinated by:

THE UNIVERSITY OF MANCHESTER

United Kingdom

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