Functional Repertoire of the Gut Microbiome in a Mouse Colon Cancer Model

Colorectal Cancer in Mice with Mutations in TGFβ signaling genes
Mutations in Transforming Growth Factor-β (TGFβ) signaling genes account for 30% of the known mutations associated with human colorectal cancer (CRC) 5–7. Yet, the role of genes in this pathway and the mechanisms involved in CRC are not clear. Mouse CRC models with mutations in this pathway require the presence of Helicobacter spp-induced inflammation in the gut to induce CRC. Thus, CRC is only induced in mice with both a genetic predisposition (through mutations in TGFβ signaling genes) and specific microbes in the gut (Helicobacter). To better understand the crosstalk between gut epithelial cells in the host and associated microbial gut community, a systems level analysis of microbial functional capacity (via metagenomics) and expression (via metatranscriptomics) is needed. To address this, we use metagenomic datasets from mouse models with/without mutations in TGFβ signaling genes and in the presence/absence of known colonic inflammatory factors (Helicobacter). We interlink these large-scale -omics datasets ( > 1TB of data) with functional annotations and metabolic pathways to better understand the role of microbes in colon cancer. This work is in collaboration with Dr. Tom Doetschman of the UA College of Medicine.