Projects Offered
Roopesh Anand Petra Beli Dorothee Dormann Thomas Hofmann René Ketting Carlotta Martelli Christof Niehrs_Ageing Christof Niehrs_Bioinfo Christof Niehrs_4R Sandra Schick Helle Ulrich Andreas Wachter Johannes Mayer_DCMem Johannes Mayer_DCSkin Wolfram Ruf Tim Sparwasser Ari WaismanRegulation of genomic parasites by small non-coding RNAs
1 PhD project offered in the IPP summer call Molecular Mechanisms in Genome Stability & Gene Regulation
Scientific Background
The genomes of basically all living organisms on our planet are invaded by genetic elements called transposable elements (TEs). These TEs can be considered as parasites in our genome, although they also contribute to proper gene regulation and other aspects of normal cellular homeostasis. TEs tend to be most active in the germ cells, as their activity in these cells will be remembered in new generations. Hence, the control of these elements is particularly important in these cells. One of the major defense mechanisms that helps to keep TEs in check is known as the piRNA pathway. This mechanism is driven by small non-coding RNAs (piRNAs) that help to guide the effector proteins to their targets in a sequence specific manner. Hence, deciding which RNAs will be turned into piRNAs is a crucial step. How piRNA precursor transcripts are selected and processed is poorly understood in vertebrates. This project will help address that lack of insight.
PhD Project: Biogenesis of small RNA precursors
The basics of the piRNA system in zebrafish have been described by us in past work. However, studies on piRNA precursors have been hampered by a number of technical aspects. In the past years, we have developed a reporter system, based on GFP silencing, that helps us study piRNA activity in this animal. At the same time, it provides insights into piRNA precursor biology. In this DFG-funded project you will study the generation and nuclear export of piRNA precursor transcripts in zebrafish. To do so you will use a combination of genetics, genomics and proteomics. This will reveal fundamental aspects of nuclear RNA export in general, and piRNA specific aspects in particular. This project will also make use of long read RNA/DNA sequencing, as the loci you will study are very repetitive and hard to study using standard NGS methods. In addition, this may reveal the potential involvement of RNA modifications in piRNA precursor biogenesis and processing. Finally, in a sideline to this project, you will work to develop the piRNA reporter system into a genetic tool for studying maternally provided transcripts, that help the development of the early embryo.
If you are interested in this project, please select Ketting as your group preference in the IPP application platform.
Publications relevant to this project
Consorte A, El Sherif Y, Kielisch F, Wittkopp N, Ketting RF (2024) Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c. bioRxiv. 10.04.615777 Link
Redl S, de Jesus Domingues AM, Caspani E, Möckel S, Salvenmoser W, Mendez-Lago M, Ketting RF (2021) Extensive nuclear gyration and pervasive non-genic transcription during primordial germ cell development in zebrafish. Development. Jan 20;148(2):dev193060. Link
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. Aug 6;46(3):285-301.e9. Link
Kaaij LJ, Mokry M, Zhou M, Musheev M, Geeven G, Melquiond AS, de Jesus Domingues AM, de Laat W, Niehrs C, Smith AD, Ketting RF (2016) Enhancers reside in a unique epigenetic environment during early zebrafish development.Genome Biol. Jul 5;17(1):146. Link
Huang HY, Houwing S, Kaaij LJ, Meppelink A, Redl S, Gauci S, Vos H, Draper BW, Moens CB, Burgering BM, Ladurner P, Krijgsveld J, Berezikov E, Ketting RF (2011) Tdrd1 acts as a molecular scaffold for Piwi proteins and piRNA targets in zebrafish. EMBO J. Jul 8;30(16):3298-308. Link
Kamminga LM, Luteijn MJ, den Broeder MJ, Redl S, Kaaij LJ, Roovers EF, Ladurner P, Berezikov E, Ketting RF. (2010) Hen1 is required for oocyte development and piRNA stability in zebrafish.EMBO J. Nov 3;29(21):3688-700. Link
Houwing S, Berezikov E, Ketting RF (2008) Zili is required for germ cell differentiation and meiosis in zebrafish.EMBO J. Oct 22;27(20):2702-11. Link
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. Apr 6;129(1):69-82. Link
