SEMINAR SERIES IGF : PHYSIOLOGY LECTURES

Séminaire externe
ico.physio
Date: 2017-04-27 10:00

Lieu: AMPHI GENOPOLYS  |  Ville: Montpellier, France

CRISPR AND TRANSPOSON BASED APPROACHES FOR HIGH-THROUGHPUT FUNCTIONAL CANCER GENOMICS IN MICE

Roland RAD
(Technische Universität München, Munich, Germany)

Roland est un expert en génomique fonctionnelle des tumeurs endocrines.
Quelques unes de ses dernières pubs:
1) Friedrich et al. Genome-wide transposon screening and quantitative insertion site sequencing for cancer gene discovery in mice. Nat Protoc. 2017 Feb;12(2):289-309. 2) Lange S, Saur D, Rad R. siRNA-coupled nanoparticles for improved therapeutic targeting of pancreatic cancer. Gut. 2016 Jul 19. pii: gutjnl-2016-312092. doi: 10.1136/gutjnl-2016-312092. 3) Maresch et al. Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice. Nat Commun. 2016 Feb 26;7:10770. doi: 10.1038/ncomms10770. 4) Weber et al. CRISPR/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice. Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13982-7.

Mouse transgenesis has provided fundamental insights into the molecular basis of cancer, but is limited by the long duration of allele/model generation and the scarcity of technologies for genetic screening. We have developed transposon tools in mice that allow the discovery of cancer drivers, which are difficult to identify with other approaches to cancer genome analysis (e.g. transcriptionally and epigenetically dysregulated genes or downstream targets of human cancer genes). Ongoing screens in mice are currently creating comprehensive catalogues of drivers for various solid and haematologic cancers, thus complementing the sequencing-based census of human cancer genes. The models can also be used to uncover mechanisms of tumour evolution, metastatic spread or treatment resistance directly in vivo, in a high-throughput manner, on a genome-wide scale. We also developed CRISPR/Cas9-based protocols for somatic gene editing in mice. In vivo transfection allowed highly multiplexed CRISPR/Cas9 delivery to digestive tract organs. We provided proof of principle applications, including direct in vivo chromosome engineering, genetic screening and cancer gene validation. These CRISPR and transposon-based approaches are substantially facilitating gene discovery and in vivo functional annotation.

 

 

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34090 Montpellier, France

 

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