Diversity of Small RNA Biology in Germ Cells

1 PhD projects offered in the IPP summer call 2019

Scientific Background

In 1998 remarkable experiments were published describing the extremely strong silencing activities of double stranded RNA. This phenomenon was named RNA interference, or RNAi, and the discoverers were awarded the Nobel Prize in 2006. Research by many teams, including ours, has demonstrated that RNAi comes in many flavors, but generally serves to recognize and to silence molecular parasites. It basically serves as a cell’s molecular immune system. Many of these parasites, such as transposons and retro-viruses, can integrate into the genome of its host. As such, these elements pose a threat to genome stability and thus have to be tightly controlled. Silencing of these invaders through RNAi can occur through destruction of RNA transcripts originating from them and through the packaging of their genomic copies into a transcriptionally non-productive form of chromatin: heterochromatin.  Although much progress has been made, we still understand very little about these processes. How does a cell recognize self from non-self? How does RNAi trigger the formation of heterochromatin? And how are these processes integrated with the rest of the cell’s programs? How is silencing information transmitted across generations? How do new silencing targets get wired into the network? We aim to answer these questions by studying RNAi related processes in model systems like Caenorhabditis elegans (a small nematode), the zebrafish and a germ cell-culture system from the silk moth, Bombyx mori.

PhD project proposal: Diversity of Small RNA Biology in Germ Cells

Possibilities exist for PhD studies in my laboratory, especially to start up a research project that compares small RNA mechanisms among different nematode species, in order to develop a better evolutionary understanding of how these pathways work and what exactly they do. 

In particular, we will study small RNA populations in different nematode species and/or natural isolates of C. elegans, with a strong focus on the germline. This will be combined with mechanistic studies on one particular protein, GTSF-1, as we find this protein has different functions in different animals, but still always connected to small RNA pathways. The aim is to make use of the variation generated by nature, to derive deeper insights into the mechanisms and functions of small RNA driven gene-regulatory pathways. These studies will also attempt to connect to gene regulatory studies in different nematodes in tight collaboration with another research group at the IMB, that of Falk Butter. Experience with C. elegans handling is not a pre-requisite.

Publications relevant to the projects

Almeida MV, de Jesus Domingues AM, Ketting RF (2019). Maternal and zygotic gene regulatory effects of endogenous RNAi pathways. PLoS Genet. 15(2):e1007784. doi: 10.1371/journal.pgen.1007784.

Almeida MV, Andrade-Navarro MA, Ketting RF (2019). Function and Evolution of Nematode RNAi Pathways. Noncoding RNA. 5(1). pii: E8. doi: 10.3390/ncrna5010008.

Roovers EF, Kaaij LJT, Redl S, Bronkhorst AW, Wiebrands K, de Jesus Domingues AM, Huang HY, Han CT, Riemer S, Dosch R, Salvenmoser W, Grün D, Butter F, van Oudenaarden A, Ketting RF. (2018) Tdrd6a Regulates the Aggregation of Buc into Functional Subcellular Compartments that Drive Germ Cell Specification. Dev Cell. 46(3):285-301.

Almeida MV, Dietz S, Redl S, Karaulanov E, Hildebrandt A, Renz C, Ulrich HD, König J, Butter F, Ketting RF. (2018)  GTSF-1 is required for formation of a functional RNA-dependent RNA Polymerase complex in Caenorhabditis elegans. EMBO J. 37(12). pii: e99325

de Albuquerque BF, Placentino M, Ketting RF. (2015)  Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans. Dev Cell. 34(4):448-56.

de Albuquerque BFM, Luteijn MJ, Cordeiro Rodrigues RJ, van Bergeijk P, Waaijers S, Kaaij LJT, Klein H, Boxem M and Ketting RF (2014). PID-1 is a novel factor that operates during 21U-RNA biogenesis in Caenorhabditis elegans. Genes Dev. 28(7):683-8

Luteijn MJ and Ketting RF (2013)PIWI-interacting RNAs: from generation to transgenerational epigenetics. (Review) Nature Reviews Genetics, 14(8):523-34

van Wolfswinkel JC, Claycomb JM, Batista PJ, Mello CC, Berezikov E, Ketting RF (2009) CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs.Cell 139(1):135-148

Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A, van den Elst H, Filippov DV, Blaser H, Raz E, Moens CB, Plasterk RH, Hannon GJ, Draper BW, Ketting RF (2007). A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 129(1):69-82

Contact Details

Prof. René Ketting

Email

Webpage: www.imb.de/research/ketting/