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Small RNA Mediated Epigenetics in Vertebrates

Objective

Since the discovery of RNAi small RNA molecules have been under intense study. They have been shown to impact many different processes, ranging from development to organ function and carcinogenesis. Recently, it has become clear that many distinct small RNA families exist. However, all act through a member of the well-conserved Argonaute family of proteins. I try to understand how specificity of the different Argonaute proteins is achieved, and I am particularly interested in Argonautes that may contribute to the epigenetic marking of genomic DNA in animals. My focus is on Argonaute function in the vertebrate germline, a tissue that is an especially intriguing system with regard to the resetting and establishment of epigenetic marks. As model system I use the zebrafish. Piwi proteins are Argonaute proteins that in vertebrates are specifically expressed in germ cells, and have been implicated in modifying chromatin structures. We demonstrated that zebrafish piwi is expressed in both the male and the female gonad and that loss of piwi results in loss of germ cells due to apoptosis. We have characterized small RNAs that bind to piwi (piRNAs) in both ovary and testis, and found that they play a role in the silencing of transposable elements. Furthermore, we have shown that the biogenesis of piRNAs differs markedly from that of other small RNAs like miRNAs. The experiments I propose address how Piwi proteins and piRNAs act in germ cells to ensure a functional germline and a stable propagation of intact chromatin over generations. First, I will address the biogenesis of piRNAs. Second, I will identify novel components of the Piwi pathway. Third, I will address the mode(s) of action of piRNAs. On all fronts a combination of genetics, molecular biology and biochemistry will be used.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/rna
  • /natural sciences/biological sciences/genetics and heredity
  • /natural sciences/biological sciences/molecular biology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/biochemistry

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH
Address
Ackermannweg 4
55128 Mainz
Germany
Activity type
Research Organisations
EU contribution
€ 264 865
Principal investigator
René Ketting (Prof.)
Administrative Contact
Franziska Hornig (Ms.)

Beneficiaries (2)

INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH
Germany
EU contribution
€ 264 865
Address
Ackermannweg 4
55128 Mainz
Activity type
Research Organisations
Principal investigator
René Ketting (Prof.)
Administrative Contact
Franziska Hornig (Ms.)
KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW

Participation ended

Netherlands
EU contribution
€ 705 135
Address
Kloveniersburgwal 29 Het Trippenhuis
1011 JV Amsterdam
Activity type
Other
Administrative Contact
Don Van Velzen (Mr.)