P16 Gulder, Sieber, Zeller
Functional characterization of carcinogenic and inflammatory secondary metabolites from the intestinal microbiota
Principal Investigators:
Gulder, Tobias, TUD
Sieber, Stephan, TUM
Zeller, Georg, EMBL
P16 will systematically identify biosynthetic gene clusters (BGCs) in gut microbiota through in silico mining of genomic and metagenomic resources. To infer pro-inflammatory or carcinogenic effects of the encoded metabolites, we will determine statistical enrichment in metagenomes of colorectal cancer and inflammatory bowel disease patients. Promising candidate BGCs will be cloned, heterologously expressed and the produced metabolites isolated and structurally as well as functionally characterized. Particular emphasis will be on compounds with heterocyclic structural elements, as these often possess significant cytotoxic activity. We will focus on the elucidation of their cellular targets as well as the corresponding modes of action via chemical proteomics. The impact of the identified biologically relevant metabolites on the host will be evaluated in animal models collaborating with partners of the CRC 1371. Ultimately, this project will elucidate new links between gut microbial metabolism and disease development in the host.
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