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Identification and characterization of novel human telomere-related biomarkers that aid cancer management by improving patient diagnosis, treatment selection, response monitoring, and drug development

Objective

Telomeres are DNA-nucleoprotein structures that protect the ends of human chromosomes through the formation of a ‘cap’ that prevents exonucleolytic degradation, inter- & intra-chromosomal fusion and subsequent chromosomal instability. Telomerase, the ribonucleoprotein enzyme that maintains linear chromosomal DNA ends by the addition of TTAGGG repeats, is completely repressed or present only at low, tightly regulated levels in normal human cells as a safeguard against cancer. Normally, telomere shortening in the absence of sufficient telomerase leads to telomere uncapping, activation of a DNA damage response, and either replicative senescence or apoptosis. Paradoxically, however, under certain conditions (when damage response pathways are defective, eg through p53 gene mutation) unchecked telomere shortening can generate a chronic genomic instability that drives and accelerates clonal evolution and cancer progression. As a result, telomeres are dysfunctional in human cancers. Individual protein components of the core telomere higher-order structure (known as the telosome, or the ‘shelterin’ complex) represent highly promising candidates for novel biomarkers of telomere dysfunction and human cancer progression. In this project (‘TeloMarker’) we have assembled the most experienced and talented scientists in telomere biology in the EU into a collaborative research consortium that will identify, characterize and validate novel telomere-related biomarkers. Biomarker discovery will be based both on known telosomal components and newly discovered affiliated proteins, as well as on telomerase and its recruitment factors. Novel telomere-related cancer biomarkers promise radically to improve early diagnosis, patient treatment selection, prognostic evaluation, and outcome monitoring, as well as furnishing new molecular targets for the development of novel small molecule anti-cancer drugs.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/chromosome
  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

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

Funding Scheme

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

Coordinator

BRUNEL UNIVERSITY LONDON
Address
Kingston Lane
UB8 3PH Uxbridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 663 597
Administrative Contact
Teresa Waller (Ms.)

Participants (7)

UNIVERSITY OF GLASGOW
United Kingdom
EU contribution
€ 312 000
Address
University Avenue
G12 8QQ Glasgow
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Joe Galloway (Mr.)
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland
EU contribution
€ 313 199
Address
Batiment Ce 3316 Station 1
1015 Lausanne
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Joachim Lingner (Prof.)
UNIVERSITAETSKLINIKUM FREIBURG
Germany
EU contribution
€ 312 000
Address
Hugstetter Strasse 49
79106 Freiburg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Gerhard Henninger (Dr.)
UMEA UNIVERSITET
Sweden
EU contribution
€ 312 000
Address
Universitetomradet
901 87 Umea
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Göran Roos (Prof.)
FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
Spain
EU contribution
€ 313 400
Address
Calle Melchor Fernandez Almagro 3
28029 Madrid
Activity type
Research Organisations
Administrative Contact
Juan Jose Collazo Nieto (Mr.)
ECOLE NORMALE SUPERIEURE DE LYON
France
EU contribution
€ 311 294
Address
Parvis Rene Descartes 15
69342 Lyon
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Valerie Tessier (Ms.)
UNIVERSITAET ULM
Germany
EU contribution
€ 311 000
Address
Helmholtzstrasse 16
89081 Ulm
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Rainer Jerg (Mr.)