ABOUT THE RESEARCHER

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

PUBLICATIONS

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  1. Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons. Proc Natl Acad Sci U S A. 2020 03 17; 117(11):5987-5996. View abstract
  2. 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
  3. RNA Interference and MicroRNA-Mediated Silencing. Curr Protoc Mol Biol. 2015 Oct 01; 112:26.1.1-26.1.5. View abstract
  4. Endogenous RNAi pathways in C. elegans. WormBook. 2014 May 07; 1-49. View abstract
  5. 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
  6. 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
  7. PIWI associated siRNAs and piRNAs specifically require the Caenorhabditis elegans HEN1 ortholog henn-1. PLoS Genet. 2012; 8(4):e1002616. View abstract
  8. 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
  9. 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
  10. Small RNA-mediated gene silencing pathways in C. elegans. Int J Biochem Cell Biol. 2010 Aug; 42(8):1306-15. View abstract
  11. 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
  12. Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7. Nature. 2008 Sep 25; 455(7212):491-6. View abstract
  13. 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
  14. Continuous exchange of sequence information between dispersed Tc1 transposons in the Caenorhabditis elegans genome. Genetics. 2003 May; 164(1):127-34. View abstract