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HER Imaging and Molecular Interaction Mapping in Breast Cancer

Objectif

The aim is to develop tools for imaging and characterising protein/protein and protein/RNA interactions in cancer using Designed Ankyrin Repeat Proteins (DARPins). DARPins are small, ultrahighly stable, antibody-like proteins that bind specific targets with high affinity in monovalent form and are readily engineered for site-specific chemical modification. The exemplar protein family will be EGFR, with focus on HER2-mediated processes in cancer.
1. EGFR-reactive DARPins will be used to characterise HER2 homo- and hetero-dimers using 4 novel technologies: Single Molecule Fluorescence, Proximity Ligation, super-resolution microscopy and FRET/FLIM. The collected data will be analysed with information on clinical outcome to determine which HER2 interactions are associated with resistance to HER2 targeted treatments.
2. Protein/RNA complexes will be isolated and characterised. These complexes may be new biomarkers for breast cancer and their characterisation is aimed at elucidating mechanisms of transcriptional regulation in response to anti-HER2 treatment.
3. Protein networks associated with EGFR signalling by imaging clusters of at 50-100 different proteins in a single cell or tissue section. This will be achieved with a robot, using large dye-conjugated tag libraries, and automatically bleaching a dye after imaging and re-labelling with another.
4. Whole body imaging (Phase I/II) clinical trial will use radiolabelled anti-HER2 DARPins to improve specificity and sensitivity of quantitative PET/SPECT/CT. The trial aims to image HER2 positive metastatic cancer and provide circulating tumour cells (CTCs) and biopsies for more detailed analysis.
5. Multivariate data obtained by the new technologies will be analysed with a range of bioinformatic tools, including artificial neural network methods, to determine novel biomarkers that aim to classify breast cancer patients at an individualised level.
The outcome is to increase the tool panel of clinicians.

Appel à propositions

FP7-HEALTH-2010-two-stage
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Coordinateur

UCL Elizabeth Garrett Anderson Institute for Women’s Health
Adresse
Gower Street
WC1E 6BT London
United Kingdom

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Type d’activité
Higher or Secondary Education Establishments
Contact administratif
Greta Borg-Carbott (Ms.)
Contribution de l’UE
€ 1 678 111

Participants (10)

NOVAMEN SAS

Participation terminée

France
Contribution de l’UE
€ 193 372
Adresse
Rue De La République 69
69002 Lyon

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Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contact administratif
Marie-Laure Muiras (Dr.)
University of Zurich
Suisse
Contribution de l’UE
€ 1 057 073
Adresse
Ramistrasse 71
8006 Zurich

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Type d’activité
Higher or Secondary Education Establishments
Contact administratif
Andreas Plueckthun (Prof.)
KING'S COLLEGE LONDON
United Kingdom
Contribution de l’UE
€ 635 749
Adresse
Strand
WC2R 2LS London

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Type d’activité
Higher or Secondary Education Establishments
Contact administratif
Tony Ng (Dr.)
TOPOSNOMOS LTD
United Kingdom
Contribution de l’UE
€ 435 454,75
Adresse
Caldervale Road The Picasso
WF1 5PF Wakefield

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Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contact administratif
Walter Schubert (Dr.)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Allemagne
Contribution de l’UE
€ 394 300
Adresse
Hofgartenstrasse 8
80539 Munchen

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Type d’activité
Research Organisations
Contact administratif
Manfred Messerschmidt (Mr.)
UPPSALA UNIVERSITET
Suède
Contribution de l’UE
€ 545 736
Adresse
Von Kraemers Alle 4
751 05 Uppsala

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Type d’activité
Higher or Secondary Education Establishments
Contact administratif
Anders Alderborn (Dr.)
Innovative Technologies in Biological Systems
Espagne
Contribution de l’UE
€ 417 600
Adresse
Parque Tecnologico De Bizkaia 502-1
48160 Derio

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Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contact administratif
Salado Clarisa (Dr.)
FIRALIS
France
Contribution de l’UE
€ 326 194
Adresse
Rue Du Fort 35
68330 Huningue

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Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contact administratif
Hüseyin Firat (Prof.)
MEDIPOLIS GMP OY

Participation terminée

Finlande
Adresse
Kiviharjuntie
90220 Oulu

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Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contact administratif
Ashesh Kumar (Dr.)
ACIES Consulting Group SAS
France
Adresse
Rue De La République 69
69002 Lyon

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Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contact administratif
Marie-Laure Muiras (Dr.)