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: 7/29/2015



Publications

For a complete listing of publications click here.

 


 

Liu Y, PC Breen and G Ruvkun 2014. Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature. 2014 Apr 17;508(7496):406-10. doi: 10.1038/nature13204. Epub 2014 Apr 2. PMCID: PMC4102179

Garcia SMDA, Y Tabach, G Lourenço, and G Ruvkun 2014. Identification of genes in toxicity pathways of trinucleotide-repeat RNA in C. elegans. Nature Structural and Molecular Biology, 2014 Aug;21(8):712-20. doi: 10.1038/nsmb.2858. Epub 2014 Jul 20.PMID: 25038802. PMCID: PMC4125460

Kirienko NV, FM Ausubel, and G Ruvkun 2015. Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A., 2015 Feb 10;112(6):1821-6. doi: 10.1073/pnas.1424954112. Epub 2015 Jan 26. PMCID: PMC4330731

Phillips, CM, K Brown, B Montgomery, T Montgomery, Gary Ruvkun. 2015. piRNAs and piRNA-dependent siRNAs protect conserved and essential C. elegans genes from misrouting into the RNAi pathway. Developmental Cell, in press.

Govindan JA, E Jayamani, X Zhang, P Breen, J Larkins-Ford, E Mylonakis and G Ruvkun. 2015. Surveillance of C. elegans translation couples via lipid signaling to systemic detoxification. Nature Cell Biology, in press.



© 2015 by the President and Fellows of Harvard College