Genome-wide in vivo screens for immune signaling components in intestinal cancer

  

Project Summary


To discover hitherto unknown immune signalling components promoting intestinal tumorigenesis, we propose to conduct genome-wide genetic screens in mice. Using our PiggyBac transposon tools, we will perform insertional mutagenesis in four intestinal cancer subentities. Newly discovered immune signalling genes will be functionally validated using CRISPR/Cas9 somatic genome engineering in mice. In addition, transcriptome-based analyses of up to 1000 transposon-induced tumors will discover genotype-immunophenotype relationships. These studies will provide comprehensive insights into the landscapes of cell-intrinsic and extrinsic immune signalling components in intestinal cancer.