Genetic screens in intestinal/colon organoid (mini-gut) culture using the CRISPR-Cas9 system.

Protein degradation via the ubiquitin-proteasome system is a key cellular mechanism that regulates protein activity. Specificity of this pathway is granted by an F-box protein, and to date, more than 70 F-box proteins have been found within mouse and human genomes. A number of critical pathways, such as cell growth/survival/death are regulated by F-box proteins and mutations in these proteins are often implicated in cancers. Around 10 to15% of colorectal cancers share a mutation in a common F-box protein. Genetic studies of these proteins are incomplete owing to the size of this protein family and in vivo studies are not always possible due to embryonic lethality of knockout mutations.