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DECRYPT Report Summary

Project ID: 339579
Funded under: FP7-IDEAS-ERC
Country: France

Mid-Term Report Summary - DECRYPT (Decrypting signals in the crypt.)

DECRYPT aims at decrypting the molecular dialogue established between the microbiota and the host, while keeping a balance with the study of pathogens, both analyzed at their interface with the gut mucosa to further our knowledge of the homeostatic and pathogenic mechanisms that characterize a healthy and a diseased gut. The intestinal crypt is a key location to study this dialogue because it harbors the stem cells, the differentiation and transit amplifying/proliferative compartments that are essential for epithelial regeneration at homeostasis, and restitution following various cytotoxic aggressions. It is also embedded in a niche of immune cells that participate in homeostatic and pathological processes under microbial stimuli. Thus, more specifically, DECRYPT has engaged in demonstrating that crypt homeostasis depends on signals “emitted” by the microbiota. At homeostasis, these signals are strongly protective of the stem cells and their niche, but alteration of these signals correlates with pathological situations such as colorectal cancer. DECRYPT is also currently demonstrating that the crypt is targeted by enteric pathogens like Shigella and Salmonella, thus providing an interesting novel paradigm to study pathogenesis.
DECRYPT has been marked by a major investment in comparative genomics, metataxonomics/metagenomics at all levels, thanks to the hiring of a bioinformatician now “embedded” in the group. It has also integrated and applied novel more resolutive methods in imaging and cell sorting, as well as high-throughput approaches, whenever necessary. It has also developed and largely used ex vivo approaches such as organoids, primary cell and tissue explants, thereby limiting animal experiments whenever possible.


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