ZF-CANCER

Developing high-thoughput bioassays for human cancers in zebrafish

 Coordinatore UNIVERSITEIT LEIDEN 

 Organization address address: RAPENBURG 70
city: LEIDEN
postcode: 2300 RA

contact info
Nome: Ton
Cognome: Brouwer
Email: send email
Telefono: +31 71 527 3149
Fax: +31 71 527 5269

 Nazionalità Coordinatore Netherlands [NL]
 Sito del progetto http://www.science.leidenuniv.nl/index.php/ibl/mcb/research_themes/zf_cancer
 Totale costo 4˙197˙454 €
 EC contributo 2˙991˙793 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2007-A
 Funding Scheme CP-FP
 Anno di inizio 2008
 Periodo (anno-mese-giorno) 2008-04-01   -   2011-03-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITEIT LEIDEN

 Organization address address: RAPENBURG 70
city: LEIDEN
postcode: 2300 RA

contact info
Nome: Ton
Cognome: Brouwer
Email: send email
Telefono: +31 71 527 3149
Fax: +31 71 527 5269

NL (LEIDEN) coordinator 0.00
2    BIOBIDE S.L.

 Organization address address: PASEO MIKELETEGI 58
city: SAN SEBASTIAN
postcode: 20009

contact info
Titolo: Mr.
Nome: Carlos
Cognome: Iguiñiz
Email: send email
Telefono: +34 94 330 9360
Fax: +34 94 330 9370

ES (SAN SEBASTIAN) participant 0.00
3    FUNDACIO PRIVADA CENTRE DE MEDICINA REGENERATIVA DE BARCELONA

 Organization address address: Dr. Aiguader 88
city: BARCELONA
postcode: 8003

contact info
Titolo: Mr.
Nome: Miguel
Cognome: Gomez-Clares
Email: send email
Telefono: +34 93 316 0320
Fax: +34 93 3160301

ES (BARCELONA) participant 0.00
4    GALAPAGOS

 Organization address address: Generaal De Wittelaan L11 A3
city: MECHELEN
postcode: 2800

contact info
Titolo: Ms.
Nome: Phia
Cognome: Van Zelst
Email: send email
Telefono: +31 71 7506765
Fax: +31 71 7506701

BE (MECHELEN) participant 0.00
5    Institute of Science and Technology Austria

 Organization address address: Am Campus 1
city: Klosterneuburg
postcode: 3400

contact info
Titolo: Mr.
Nome: Bruno
Cognome: Woeran
Email: send email
Telefono: +43 2243 9000 1038
Fax: +43 2243 9000 2000

AT (Klosterneuburg) participant 0.00
6    KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW

 Organization address address: KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
city: AMSTERDAM
postcode: 1011 JV

contact info
Titolo: Mr.
Nome: Don
Cognome: Van Velzen
Email: send email
Telefono: +31 30 2121800
Fax: +31 30 2121865

NL (AMSTERDAM) participant 0.00
7    MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.

 Organization address address: Hofgartenstrasse 8
city: MUENCHEN
postcode: 80539

contact info
Titolo: Dr.
Nome: Birgit
Cognome: Knepper-Nicolai
Email: send email
Telefono: +49 351 2102772
Fax: +49 351 2101089

DE (MUENCHEN) participant 0.00
8    THE UNIVERSITY OF EDINBURGH

 Organization address address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL

contact info
Titolo: Ms.
Nome: Angela
Cognome: Noble
Email: send email
Telefono: +44 131 650 9024
Fax: +44 131 650 9023

UK (EDINBURGH) participant 0.00
9    ZF-SCREENS BV

 Organization address address: J H OORTWEG 19
city: LEIDEN
postcode: 2333 CH

contact info
Titolo: Mr.
Nome: Pieter
Cognome: Slijkerman
Email: send email
Telefono: +31 71 5274944
Fax: +31 71 5275088

NL (LEIDEN) participant 0.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

libraries    transparency    discovery    validation    throughput    model    labelled    automation    embryos    tumour    hallmarks    contains    forms    screening    vertebrate    gene    accelerate    zf    histopathological    angiogenesis    chemical    emerged    kinase    optical    human    cell    identification    drug    bioassays    tumours    rna    readouts    screened    fluorescent    interference    cancers    cancer    inhibition    profiling    bio    compounds    anti    fluorescently    tumors    time    cells    oncogenes    powerful    vivo    exploited    genetic    imaging    transparent    genome    studying    drugs    transgenic    fundamental    progression    zebrafish   

 Obiettivo del progetto (Objective)

'Recently the zebrafish has emerged as a new important system for cancer research because the zebrafish genome contains all orthologs of human oncogenes and forms tumors with similar histopathological and gene profiling features as human tumors. The zebrafish provides an in vivo vertebrate model for identifying novel mechanisms of cancer progression and for development of new anticancer compounds in a time- and cost-effective manner. The ZF-CANCER project aims to develop high-throughput bioassays for target discovery and rapid drug screenings applicable in preclinical validation pipelines. Fluorescently labelled human and zebrafish cancer cells will be implanted (xenogenic and allogenic transplantation) into zebrafish embryos transgenic for a GFP-vascular marker and quantitative, multi-colour fluorescent intravital bio-imaging of tumour progression will be set up as the readout. Because of its amenability to genetic manipulation and optical transparency, the zebrafish is currently the only vertebrate model that allows the simultaneous in vivo imaging of all hallmarks of cancer progression including cell survival, proliferation, migration and induction of angiogenesis. The combination of visual, non- invasive monitoring in translucent host embryos with powerful RNA interference technology, successfully developed for human cancer cells will enable identification of novel targets in a wide variety of human cancers. Automation of these fluorescent readouts will accelerate the screening process with chemical libraries to discover new compounds involved in different aspects of cancer progression and inhibition. In the case study, a selected panel of genes and lead compounds will be screened on a high-throughput platform, possibly resulting in the identification of important anti-tumour drugs relevant for human cancer therapy. Fundamental knowledge, tools and technical expertise gained from ZF-CANCER will be commercially exploited by one company and two high-tech SMEs.'

Introduzione (Teaser)

An alternative animal model based on zebrafish was developed for studying cancer progression and identifying drug targets and anti-cancer lead compounds. The ZF-Cancer model holds the potential to speed up the screening of anti-cancer therapies.

Descrizione progetto (Article)

Zebrafish have emerged as a new model for studying oncogenesis, mainly because its genome contains all orthologues of human oncogenes and forms tumours with similar histopathological and gene profiling features to human tumours. Additionally, the availability of many transgenic zebrafish combined with their optical transparency make it a powerful model for imaging cancer progression.

The scientific objective of the EU-funded 'Developing high-thoughput bioassays for human cancers in zebrafish.' (ZF-Cancer) project was to develop clinically relevant high-throughput bioassays for cancer progression. These were envisioned to be exploited in the pre-clinical validation of novel chemical and genetic cancer targets.

This system had the major advantage of direct visualisation of tumour growth and metastasis in an optically transparent vertebrate model organism. The transparent zebrafish embryos coupled with ribonucleic acid (RNA) interference technology enabled the identification of novel gene targets that drove tumour progression in a range of cancers. The inoculation of fluorescently-labelled human cancer cells allowed for delineation of the fundamental hallmarks of cancers.

Automation of these fluorescent readouts would accelerate the process of screening of chemical libraries for the discovery of new compounds involved in different aspects of cancer progression and inhibition. To this end, these technologies were integrated in a robotic setup, thereby allowing full automation of the process from tumour cell implantation and drug treatment, to bio-imaging and data analysis.

Special emphasis was given to kinase inhibitors that sensitised p53 mutant embryos against irradiation-induced apoptosis and angiogenesis development. Potent anti-cancer kinase drug targets were discovered with this approach and pilot compounds were screened.

The ZF-Cancer zebrafish embryo model has the potential to accelerate the lead time of anti-tumour drugs considerably, rendering the entire process more cost effective and efficient. Apart from obvious benefits for research, the zebrafish model could extend to pharmaceutical-oriented applications.

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