About the Project
About the Project
3-year funded PhD – RNA modifying enzymes in development and disease
Part of EpiCrossBorders: International Helmholtz-Edinburgh Research School for Epigenetics (contact The School Office at [Email Address Removed])
This is an exciting PhD opportunity to join a well-funded collaborative PhD project. This project is a collaboration between leading research groups based at the Helmholtz Center Munich and the University of Edinburgh. The main part of the project takes place in the lab of Prof. Dr. Robert Schneider at the Helmholtz Center Munich, but will include an exchange stay in the lab of Prof. Donal O’Carrol at the University of Edinburgh.
Project description: RNA modifying enzymes in development and disease
Recent breakthroughs have transformed our understanding of the epitranscriptome and allow us now to interrogate modifications of RNA at an unprecedented scale. It became clear that RNA modifications play essential roles in the regulation of splicing, nuclear export of RNA, RNA stability and translation. The epitranscriptome constitutes a new layer of (epi)genetic information and could change the way how we look at RNA, but also open new avenues to fight cancer. We recently identified two novel RNA methyltransferases and revealed their function in vitro and in vivo, creating new mouse models for human diseases (Ignatova et al., 2020a; Ignatova et al., 2020b).
The aim of the project will be i) to identify novel methyltransferases as well as ii) to determine the function of these enzyme(s) and iii) of the respective modifications in development and disease by applying a combination of in vitro and in vivo assays. For this project we will team up with the O’ Carroll lab. We will build on the expertise of the O’Carroll lab in cellular manipulations, mouse models and the role of RNA modifications in development and during hematopoiesis as well as on our expertise in the identification of novel chromatin and RNA modifying enzymes.
This project includes the possibility to be part of a dynamic and international team and to learn state of the art technologies both in Munich and Edinburgh (such novel NGS based mapping approaches and their bioinformatic analysis, as wells as Crispr/Cas9/Cas13 mediated manipulations, advanced imaging techniques, cellular assays, biochemical approaches and in vitro assays). It requires the motivation to develop and execute the next breakthrough ideas in an interdisciplinary and scientifically stimulating environment. We will employ diverse systems such as mES cells, mouse models and human cancer cells coupled with omics, advanced biochemistry and masspectrometry to gain insights in the mechanism of action of novel RNA methyltransferases. Since multiple studies have linked RNA modifications to cancer this project has the potential to discover novel druggable targets to treat cancers.
The over-arching long-term goal is to (i) understand mechanistically how RNA modifications regulate RNA, (ii) identify novel RNA modifying pathways in order to discover new therapy targets and (iii) move the fascinating epitranscriptomics field to a new level.
More information and to apply:
All applications need to go through our application portal which you can access here: https://bit.ly/2WAG2Dx
Funding details: a three-year Doctoral contract and no tuition fees.
Eligibility: Applicants should hold a University Master’s degree (MSc or equivalent) to apply. with a strong background in biological sciences, (bio)chemistry, biomedicine computer science or related discipline, have excellent English language skills and a strong interest in an international PhD program. Your MSc degree has to include a Master Thesis on a scientific project.
Applicants still studying for their Master's degree may provide a provisional certificate or bona fide statement from the University stating the marks already obtained and estimated graduation date. Applicants accepted in the program are required to have completed their Master's degree before they can start their PhD work in the program. Applicants accepted within the program have to start their PhD work latest in fall 2022.
Applicants who wish to apply with a four-year BSc degree (equivalent to 240 ECTS) without a MSc, please contact the research School directly.
For more information and to apply please visit our website (https://www.helmholtzresearchschool-epigenetics.org).
Enquiries can be made by email ([Email Address Removed])
Deadline for applications: 15th October 2021
Start date: 1st October 2022
References
Ignatova, V.V., Kaiser, S., Sook Yuin, S., Bing, X., Stolz, P., Tan, Y.X., Xim Tan, Y., Leng Lee, C., Hoon Gay, F.P., Rico Lastres, P.,Gerlini, R., Rathkolb, B., Aguilar-Pimentel., A. Sanz-Moreno, A., Klein-Rodewald, T., Calzada-Wack, J.,Ibragimov, E., Valenta, M., Lukauskas, S., Marscha, S., Leuchtenberger, S., Fuchs, H., Gaius-Durner, V., Hrabe de Angelis, M., Bultmann, S., Rando, O.J., Guccione, E., Kellner, S.M. and Schneider, R. (2020). METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth. Science Advances, 6, eaaz4551
Zoch, A., Auchynnikava, T., Berrens, R. V., Kabayama, Y., Schöpp, T., Heep, M., Vasiliauskaitė, L., Pérez-Rico, Y. A., Cook, A. G., Shkumatava, A., Rappsilber, J., Allshire, R. C. and O'Carroll, D. (2020). SPOCD1 is an essential executor of piRNA-directed 1 de novo DNA methylation. Nature 584, 635-639.
Ignatova, V.V., Stolz, P., Kaiser, S., Gustafsson, T.H., Rico Lastres, P., Sanz-Moreno, A., Cho, Y.L., Amarie, O.V., Aguilar-Pimentel, A., Klein-Rodewald, T., Calzada-Wack, J., Becker, L., Marschall, S., Kraiger, M., Garrett, L., Seisenberger, C., Hölter, S.M., Borland, K., Van De Logt, E., Jansen, P., Baltissen, M.P., Vermeulen, M., Wurst, W., Gailus-Durner, V., Fuchs, H., Hrabe de Angelis, M., Rando, O.J., Kellner, S.M., Bultmann, S. and Schneider. R. (2020). The rRNA m6A methyltransferase METTL5 regulates pluripotency and developmental programmes. Genes and Development , 34, 715-729.
Morgan, M., Much, C., DiGiacomo, M., Azzi, C., Ivanova, I., Vitsios, D. M., Pistolic, J., Collier, P., Ventura De Oliveira Moreira, P., Benes, V., Enright, A. J. and O'Carroll, D. (2017). mRNA 3ʹ uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome Nature 548, 347-351.
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