BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Max Perutz Lecture 2014: C. elegans surveillance of conserved cell ular components to detect and defend pathogen attacks\, real or imagined - Gary Ruvkun\, MGH Harvard DTSTART:20141205T161500Z DTEND:20141205T180000Z UID:TALK51147@talks.cam.ac.uk CONTACT:Scientific Meetings Co-ordinator DESCRIPTION:RNAi-based gene inactivations targeting the core cellular comp onents induce C. elegans to avoid the lawn of bacteria expressing those ge ne inactivating dsRNAs. Many of these gene inactivations that cause ave rsive behaviors encode the most conserved proteins of eukaryotes\, from th e ribosome\, mitochondria\, cytoskeleton\, and proteasome. And many are t argets of antibiotics produced by fungi and microbes. Toxins that target the same proteins also cause these aversive behaviors. C. elegans pathoge n response and detoxification cytochrome p450 genes are also induced by E. coli expressing aversive C. elegans dsRNAs or drugs. Thus C. elegans int erprets the E. coli that express just a single dsRNA that targets a C. ele gans gene encoding a ribosomal protein for example as a pathogenic bacteri a. A key prediction of this xenobiotic and bacterial virulence factor sur veillance model is that even a chromosomal mutation disrupting for example a surveilled ribosomal component will cause induction of detoxification a nd pathogen responses. As predicted\, various mutations that cause transl ation defects only in the germline induce the expression of particular cyt ochrome and ABC transporter genes in the intestine. In a functional geno mic screen for animals that now fail to express these detoxification respo nses to these germline translation defects\, that animals that are now "bl ind" to their translation defects\, we found a kinase signaling cascade to p38 MAPK and to the ZIP-2/bZip and SKN-1/Nrf2 transcription factors and u pstream steps in a lipid biosynthetic pathway. Mammalian bile acids can re scue the defect in detoxification gene induction caused by these C. elegan s lipid biosynthetic gene inactivations. Similarly\, crude hydrophobic ext racts prepared from C. elegans with translation deficits but not extracts from wild type can rescue detoxification gene induction. These bile acids are likely to be a hormonal signal of translational malaise between the g ermline and the somatic intestine. Germline translation defects induce p3 8 MAPK phosphorylation and nuclear localization in the intestine and parti cular kinase and lipid biosynthetic genes that emerged from the RNAi scree n act upstream of this\, ordering the pathway components identified. Thes e eukaryotic antibacterial countermeasures are not ignored by bacteria: we identified 3 bacterial species that actively suppress C. elegans detoxifi cation responses to ribosomal mutations.\n This screen identifies genetic components of the core cellular component surveillance systems\, the endoc rine systems of spreading the detoxification signal systemically\, and the coupling of these signals to upregulation of xenobiotic detoxification an d anti-bacterial pathogenesis systems. Human variation in the homologues of these genes may underlie aberrant upregulation of drug detoxification a nd innate immunity pathways in the absence of a toxic or pathogen\, for ex ample\, autoimmunity or feeding dysfunctions. The endocrine state of our aversively stimulated C. elegans may be homologous to the endocrine state of humans who feel unwell. The genetic suppressors of this aversive behav ior we have identified may reveal an endocrinology of feeling ill or well. \n LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC Laboratory of Molecular Biol END:VEVENT END:VCALENDAR