Overview

Genome maintenance and genome defense ensure that intact and unchanged genetic material is delivered to offspring, and that genes are properly expressed without mutations. One threat to the genome comes from transposable elements (TEs) and retroviruses, DNA elements that can potentially wreak havoc in the genome by inserting into genes, and by mediating homologous recombination. Half of the human genome is derived from transposon sequences, underscoring the need to control these elements. In addition to mutagenic properties, mis-expression of repeat elements and retroviruses can disrupt cellular homeostasis and elicit stress responses and antiviral responses. Such mis-expression has been linked to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and also to geographic atrophy (GA), an advanced form of age-related macular degeneration.

One method of defense against transposable elements employs RNA interference (RNAi), a deeply conserved genome defense mechanism that acts in organisms ranging from protist to human to recognize and suppress transposons. In non-mammalian species, RNAi also acts as an important anti-viral defense mechanism, whereas in human, viral RNA triggers the anti-viral type I interferon response.

Not all host-transposon interactions are deleterious to the host. Transposons are a major contributor to genomic plasticity; in particular, transposon activation under stress conditions can facilitate adaptation of the host in new environmental conditions by altering gene expression or gene function through transposon insertion. An extreme example of a beneficial host-transposon interaction is the repurposing of (retro)transposon proteins, e.g. the RAG1 protein that mediates V(D)J recombination and is derived from a transposase protein, and the Arc protein that mediates intercellular RNA transfer and is derived from a retrotransposon Gag protein.

Our research program focuses on the genetic and biochemical analysis of the interactions between a host and its transposable elements and viruses using the simple host organism Caenorhabditis elegans. We are interested in understanding how transposons are (mis)regulated under stress conditions, how transposable elements and viruses are silenced, and which stress responses are triggered by mis-expression of transposons, and how these responses are triggered.

Background

Sylvia Fischer receiver her Ph.D. from Utrecht University in the Netherlands and completed postdoctoral research training in genetics in the Department of Molecular Biology at Massachusetts General Hospital and the Department of Genetics at Harvard Medical School

Researcher Services

Researcher Areas

  • Host responses to viral infection and (retro)transposon activity
  • Small RNA mediated gene regulation

Research Divisions

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Newman MA, Ji F, Fischer SEJ, Anselmo A, Sadreyev RI, Ruvkun G. The surveillance of pre-mRNA splicing is an early step in C. elegans RNAi of endogenous genes. Genes Dev. 2018 05 01; 32(9-10):670-681. View abstract
  2. Fischer SE. RNA Interference and MicroRNA-Mediated Silencing. Curr Protoc Mol Biol. 2015 Oct 01; 112:26.1.1-5. View abstract
  3. Billi AC, Fischer SE, Kim JK. Endogenous RNAi pathways in C. elegans. WormBook. 2014 May 07; 1-49. View abstract
  4. Fischer SE, Pan Q, Breen PC, Qi Y, Shi Z, Zhang C, Ruvkun G. Multiple small RNA pathways regulate the silencing of repeated and foreign genes in C. elegans. Genes Dev. 2013 Dec 15; 27(24):2678-95. View abstract
  5. Zhang C, Montgomery TA, Fischer SE, Garcia SM, Riedel CG, Fahlgren N, Sullivan CM, Carrington JC, Ruvkun G. The Caenorhabditis elegans RDE-10/RDE-11 complex regulates RNAi by promoting secondary siRNA amplification. Curr Biol. 2012 May 22; 22(10):881-90. View abstract
  6. Montgomery TA, Rim YS, Zhang C, Dowen RH, Phillips CM, Fischer SE, Ruvkun G. PIWI associated siRNAs and piRNAs specifically require the Caenorhabditis elegans HEN1 ortholog henn-1. PLoS Genet. 2012; 8(4):e1002616. View abstract
  7. Fischer SE, Montgomery TA, Zhang C, Fahlgren N, Breen PC, Hwang A, Sullivan CM, Carrington JC, Ruvkun G. The ERI-6/7 helicase acts at the first stage of an siRNA amplification pathway that targets recent gene duplications. PLoS Genet. 2011 Nov; 7(11):e1002369. View abstract
  8. Zhang C, Montgomery TA, Gabel HW, Fischer SE, Phillips CM, Fahlgren N, Sullivan CM, Carrington JC, Ruvkun G. mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2011 Jan 25; 108(4):1201-8. View abstract
  9. Fischer SE. Small RNA-mediated gene silencing pathways in C. elegans. Int J Biochem Cell Biol. 2010 Aug; 42(8):1306-15. View abstract
  10. Sebastiani P, Montano M, Puca A, Solovieff N, Kojima T, Wang MC, Melista E, Meltzer M, Fischer SE, Andersen S, Hartley SH, Sedgewick A, Arai Y, Bergman A, Barzilai N, Terry DF, Riva A, Anselmi CV, Malovini A, Kitamoto A, Sawabe M, Arai T, Gondo Y, Steinberg MH, Hirose N, Atzmon G, Ruvkun G, Baldwin CT, Perls TT. RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. PLoS One. 2009 Dec 14; 4(12):e8210. View abstract
  11. Fischer SE, Butler MD, Pan Q, Ruvkun G. Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7. Nature. 2008 Sep 25; 455(7212):491-6. View abstract
  12. Vastenhouw NL, Fischer SE, Robert VJ, Thijssen KL, Fraser AG, Kamath RS, Ahringer J, Plasterk RH. A genome-wide screen identifies 27 genes involved in transposon silencing in C. elegans. Curr Biol. 2003 Aug 05; 13(15):1311-6. View abstract
  13. Fischer SE, Wienholds E, Plasterk RH. Continuous exchange of sequence information between dispersed Tc1 transposons in the Caenorhabditis elegans genome. Genetics. 2003 May; 164(1):127-34. View abstract