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Systems-Level, Multi-layer Understanding of Cellular Responses to Ionizing Radiation

Objective

The TRIREME project aims at developing and implementing a multidisciplinary strategy for a systems-level analysis of a cornerstone of cellular homeostasis – the DNA damage response (DDR). The DDR is a complex signaling network that is responsible for maintaining the stability and integrity of the cellular genome in the face of DNA damage. DDR defects underlie acute and chronic forms of human ailments that involve tissue degeneration, premature ageing, sensitivity to environmental agents and cancer predisposition. Importantly, many cancer treatment regimens are based on DNA damaging agents. Therefore, gaining systems-level understanding of the DDR is of paramount importance for human health. TRIREME brings together a multidisciplinary consortium of six world-leading researchers with long-standing expertise in the DDR, cell cycle control, functional genomics, proteomics and computational biology. It will focus on a prototypic DNA damage inducer – ionizing radiation (IR), used extensively in cancer radiotherapy. The critical IR-induced DNA lesion is the double strand break, which vigorously activates the DDR. We will systematically analyze the IR-induced network in all its major layers: gene expression, microRNA expression, the proteome, and key protein post-translational modifications. The analysis is aimed at obtaining a global view of the DDR, and identifying new players in the network. The data obtained by these different approaches will be integrated into coherent models using novel computational algorithms developed for TRIREME. To the best of our knowledge, such an analysis has not been applied before to mammalian systems. The results are expected to have far-reaching ramifications in various biomedical fields, with special importance for clinical oncology.

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /natural sciences/biological sciences/genetics and heredity/genome
  • /medical and health sciences/clinical medicine/oncology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/proteomics

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

TEL AVIV UNIVERSITY
Address
Ramat Aviv
69978 Tel Aviv
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 049 920
Administrative Contact
Lea Pais (Ms.)

Participants (4)

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 505 380
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Edna Murphy (Ms.)
USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE
Czechia
EU contribution
€ 425 000
Address
Videnska 1083
142 20 Praha 4
Activity type
Research Organisations
Administrative Contact
Jiri Bartek (Prof.)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany
EU contribution
€ 508 876
Address
Hofgartenstrasse 8
80539 Munich
Activity type
Other
Administrative Contact
Joachim Gerlach (Mr.)
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Switzerland
EU contribution
€ 439 250
Address
Raemistrasse 101
8092 Zuerich
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ruedi Aebersold (Prof.)