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Genomic determinants of inflammation: from physical measurements to system perturbation and mathematical modeling

Objective

Inflammation is a complex biochemical and cellular response essential for the viability of higher organisms because of its requirement in anti-microbial defence and protection from the consequences of tissue injury. However, uncontrolled or sustained inflammation leads to several diseases with a huge social impact, ranging from autoimmune diseases to septic shock and cancer. While the requirement for specific transcription factors (TF) in inflammatory gene transcription is known, quantitative models describing how their interactions with genomic sequences leads to normal or pathological outcomes are not available. Unravelling how genomic organization underlies the orchestrated expression of inflammatory genes is crucial to understand how to pharmacologically tune pathological inflammatory responses. Now is the right moment to tackle this question as for the first time we have genomic technologies and computational abilities to generate the necessary quantitative data and to build computational models describing spatiotemporal coordination of transcription of hundreds of inflammatory genes by multiple TFs. To implement this objective, we have assembled a consortium of top-level scientists in the European Research Area who reached documented excellence in complementary aspects of transcriptional control, namely quantitative measurement of TF-DNA interactions, in vitro and in vivo analysis of chromatin organization, manipulation of genomic sequences by homologous recombination, computational and systems biology applied to transcriptional circuits. The network provides the critical mass required to generate ample quantitative and complementary datasets describing the minimal transcriptional regulatory blocks relevant for inflammation, thus enabling the integration of their coordinated activities via systems approaches. Each research group complements the other participants and the whole projects, and as such this proposal can not be carried out on any individual level.

Field of science

  • /natural sciences/mathematics/applied mathematics/mathematical model
  • /medical and health sciences/clinical medicine/oncology/cancer

Call for proposal

FP7-HEALTH-2007-B
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Address
Wellington Square University Offices
OX1 2JD Oxford
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 485 877,45
Administrative Contact
Sue Stoneham (Ms.)

Participants (10)

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE

Participation ended

United Kingdom
EU contribution
€ 331 011,55
Address
South Kensington Campus Exhibition Road
SW7 2AZ London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Julie Williams (Ms.)
UNIVERSITE JOSEPH FOURIER GRENOBLE 1
France
EU contribution
€ 208 800
Address
Avenue Centrale, Domaine Universitaire 621
38041 Grenoble
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Leslie Hollett (Ms.)
ECOLE NORMALE SUPERIEURE DE LYON
France
EU contribution
€ 316 800
Address
46 Allee D'italie
69364 Lyon
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Valerie Tessier (Ms.)
UNIVERSITA VITA-SALUTE SAN RAFFAELE
Italy
EU contribution
€ 280 800
Address
Via Olgettina 58
20132 Milano
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Raffaella Voltolini (Dr.)
ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy
EU contribution
€ 242 400
Address
Via Filodrammatici 10
20121 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ilaria Foti (Ms.)
WEIZMANN INSTITUTE OF SCIENCE
Israel
EU contribution
€ 166 380
Address
Herzl Street 234
7610001 Rehovot
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Talia Tzahor (Ms.)
THE HEBREW UNIVERSITY OF JERUSALEM
Israel
EU contribution
€ 193 500
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Eran Vardi (Dr.)
UNIVERSITAET ZU KOELN
Germany
EU contribution
€ 349 200
Address
Albertus Magnus Platz
50931 Koeln
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Petra Schreiner-Kaub (Ms.)
OXFORD NANOPORE TECHNOLOGIES LTD
United Kingdom
EU contribution
€ 90 000
Address
Robert Robinson Avenue - Oxford Science Park 4
OX4 4GA Oxford
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jim Bruce (Dr.)
IC CONSULTANTS LTD
United Kingdom
EU contribution
€ 261 536
Address
Sherfield Building, Imperial College Of Science, Technology And Medicine
SW7 2AZ London
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Michiyo Shima (Ms.)