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D-FENS SIGNED

Dicer-Dependent Defense in Mammals

Total Cost €

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EC-Contrib. €

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Partnership

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 D-FENS project word cloud

Explore the words cloud of the D-FENS project. It provides you a very rough idea of what is the project "D-FENS" about.

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Project "D-FENS" data sheet

The following table provides information about the project.

Coordinator
USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE 

Organization address
address: VIDENSKA 1083
city: PRAHA 4
postcode: 142 20
website: www.img.cas.cz

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Czech Republic [CZ]
 Total cost 1˙950˙000 €
 EC max contribution 1˙950˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2020-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE CZ (PRAHA 4) coordinator 1˙537˙000.00
2    SLOVENSKA ZDRAVOTNICKA UNIVERZITA V BRATISLAVE SK (BRATISLAVA) participant 413˙000.00

Map

 Project objective

Viral infection or retrotransposon expansion in the genome often result in production of double-stranded RNA (dsRNA). dsRNA can be intercepted by RNase III Dicer acting in the RNA interference (RNAi) pathway, an ancient eukaryotic defense mechanism. Notably, endogenous mammalian RNAi appears dormant while its common and unique physiological roles remain poorly understood. A factor underlying mammalian RNAi dormancy is inefficient processing of dsRNA by the full-length Dicer. Yet, a simple truncation of Dicer leads to hyperactive RNAi, which is naturally present in mouse oocytes. The D-FENS project will use genetic animal models to define common, cell-specific and species-specific roles of mammalian RNAi. D-FENS has three complementary and synergizing objectives:

(1) Explore consequences of hyperactive RNAi in vivo. A mouse expressing a truncated Dicer will reveal at the organismal level any negative effect of hyperactive RNAi, the relationship between RNAi and mammalian immune system, and potential of RNAi to suppress viral infections in mammals.

(2) Define common and species-specific features of RNAi in the oocyte. Functional and bioinformatics analyses in mouse, bovine, and hamster oocytes will define rules and exceptions concerning endogenous RNAi roles, including RNAi contribution to maternal mRNA degradation and co-existence with the miRNA pathway.

(3) Uncover relationship between RNAi and piRNA pathways in suppression of retrotransposons. We hypothesize that hyperactive RNAi in mouse oocytes functionally complements the piRNA pathway, a Dicer-independent pathway suppressing retrotransposons in the germline. Using genetic models, we will explore unique and redundant roles of both pathways in the germline.

D-FENS will uncover physiological significance of the N-terminal part of Dicer, fundamentally improve understanding RNAi function in the germline, and provide a critical in vivo assessment of antiviral activity of RNAi with implications for human therapy.

 Publications

year authors and title journal last update
List of publications.
2016 Shubhada Bopegamage
Enterovirus infections: Pivoting role of the adaptive immune response
published pages: 495-497, ISSN: 2150-5594, DOI: 10.1080/21505594.2016.1175701
Virulence 7/5 2019-06-06
2016 Eliska Svobodova, Jana Kubikova, Petr Svoboda
Production of small RNAs by mammalian Dicer
published pages: 1089-1102, ISSN: 0031-6768, DOI: 10.1007/s00424-016-1817-6
Pflügers Archiv - European Journal of Physiology 468/6 2019-06-06
2016 Sravya Ganesh, Petr Svoboda
Retrotransposon-associated long non-coding RNAs in mice and men
published pages: 1049-1060, ISSN: 0031-6768, DOI: 10.1007/s00424-016-1818-5
Pflügers Archiv - European Journal of Physiology 468/6 2019-06-06
2017 Vedran Franke, Sravya Ganesh, Rosa Karlic, Radek Malik, Josef Pasulka, Filip Horvat, Maja Kuzman, Helena Fulka, Marketa Cernohorska, Jana Urbanova, Eliska Svobodova, Jun Ma, Yutaka Suzuki, Fugaku Aoki, Richard M. Schultz, Kristian Vlahovicek, Petr Svoboda
Long terminal repeats power evolution of genes and gene expression programs in mammalian oocytes and zygotes
published pages: 1384-1394, ISSN: 1088-9051, DOI: 10.1101/gr.216150.116
Genome Research 27/8 2019-06-06
2019 Tomas Demeter, Michaela Vaskovicova, Radek Malik, Filip Horvat, Josef Pasulka, Eliska Svobodova, Matyas Flemr, Petr Svoboda
Main constraints for RNAi induced by expressed long dsRNA in mouse cells
published pages: e201800289, ISSN: 2575-1077, DOI: 10.26508/lsa.201800289
Life Science Alliance 2/1 2019-05-27

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