BBS Faculty Member - Gary Ruvkun

Gary Ruvkun

Department of Genetics

Massachusetts General Hospital
Simches Research Building, CPZN 7250
185 Cambridge Street
Boston, MA 02114
Tel: 617-726-5959
Email: ruvkun@molbio.mgh.harvard.edu
Lab Members: 10 postdoctoral fellows, 2 technicians, 2 project scientists
Visit my lab page here.



Our lab uses C. elegans molecular genetics and genomics to study miRNA and RNAi pathways as well as mechanisms of aging and microbial surveillance. Using genetic and RNA interference approaches, we have identified genes that positively or negatively regulate RNAi and microRNA pathways. These genes reveal the trajectory of siRNAs and miRNAs as they target mRNAs, as well as components that may be developed as drug targets to enhance RNAi. This analysis has revealed subcellular organelles that mediate steps in the small RNA pathways.

Our genetic analysis of
C. elegans lifespan revealed a surprising surveillance of conserved core components of cells, such as the ribosome, the mitochondrion, the proteasome, and a coupling to the induction of detoxification and innate immune responses. We are now dissecting this surveillance system by isolating mutations in C. elegans that fail to recognize deficits in ribosomal, mitochondrial or proteasomal function or fail to induce detoxification responses. The drug or essential gene inactivations or mutations in the core cellular components inhibit feeding and induce an aversive behavior program. The endocrine state of these aversively stimulated animals may be homologous to the endocrine state of humans who feel unwell. Our genetic suppressors this surveillance pathway is beginning to reveal an endocrinology of feeling ill. The human homologues of the genes we identify promise to explain how humans respond appropriately and inappropriately to drugs or bacteria, or activate drug detoxification and innate immunity pathways in the absence of a triggering drug or bacteria, perhaps inducing a false endocrine state of poisoning or a false perception of infection. Variation in xenobiotic detection and response pathways may be the cause of diseases as diverse as autoimmune disorders and anorexia.



Last Update: 8/7/2014



Publications

For a complete listing of publications click here.

 


 

Caenorhabditis elegans pathways that surveil and defend mitochondria. Liu Y, Samuel BS, Breen PC, Ruvkun G. Nature. 2014 Apr 17;508(7496):406-10. doi: 10.1038/nature13204. Epub 2014 Apr 2. PMID:24695221

Multiple small RNA pathways regulate the silencing of repeated and foreign genes in C. elegans. Fischer SE, Pan Q, Breen PC, Qi Y, Shi Z, Zhang C, Ruvkun G. Genes Dev. 2013 Dec 15;27(24):2678-95. doi: 10.1101/gad.233254.113. PMID:24352423

Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence. Tabach Y, Billi AC, Hayes GD, Newman MA, Zuk O, Gabel H, Kamath R, Yacoby K, Chapman B, Garcia SM, Borowsky M, Kim JK, Ruvkun G. Nature. 2013 Jan 31;493(7434):694-8. doi: 10.1038/nature11779. Epub 2012 Dec 23. PMID:23364702

High-throughput sequencing reveals extraordinary fluidity of miRNA, piRNA, and siRNA pathways in nematodes. Shi Z, Montgomery TA, Qi Y, Ruvkun G. Genome Res. 2013 Mar;23(3):497-508. doi: 10.1101/gr.149112.112. Epub 2013 Jan 30. PMID:23363624

MUT-16 promotes formation of perinuclear mutator foci required for RNA silencing in the C. elegans germline. Phillips CM, Montgomery TA, Breen PC, Ruvkun G. Genes Dev. 2012 Jul 1;26(13):1433-44. doi: 10.1101/gad.193904.112. Epub 2012 Jun 19. PMID:22713602

Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses. Melo JA, Ruvkun G. Cell. 2012 Apr 13;149(2):452-66. doi: 10.1016/j.cell.2012.02.050. PMID:22500807



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