RNA Quality Control - Štěpánka Vaňáčová

PhD Topics

1. The role of posttranscriptional RNA modifications in cell differentiation

Supervisor: assoc.prof. Mgr. Štěpánka Vaňáčová, Ph.D.

Annotation:
The internal and external RNA modifications play crucial roles in a number of essential processes of eukaryotic organisms. They regulate the production of germ cells, cellular differentiation, response to stress, and defects in this pathway have been linked to a number of human diseases. The aim of this project is to study in details how specific terminal RNA modifications regulate cellular differentiation. As the model system, we use human cell lines derived from somatic cells as well as induced pluripotents cells. The student will master number of diverse methodical approaches, such as human cell culture manipulations (cultivation, RNAi, CRISPR/Cas9, etc.), recombinant DNA preparation, protein expression and purification, high-throughput analyses and enzymatic assays.
She/he will have the opportunity to present the results at prestigious international conferences. Moreover, this project will involve collaboration with other leading researches in European institutes. Students from our group after accomplishing their thesis typically continue in their carrier at highly prestigious institutes, such as FMI in Basel, ETH Zurich, Columbia University in New York, Stanford, etc.
Prospective student should ideally have done masters in molecular biology/biochemistry and have a laboratory experience in nucleic acids and/or protein purification and analysis. The most highly valued feature will however be excitement for science and strong drive in tackling important biological questions.

Recommended literature:
Zigáčková, D., Vaňáčová, Š. 2018 The role of 3′ end uridylation in RNA metabolism and cellular physiology
Phil. Trans. R. Soc. B 373 20180171; DOI: 10.1098/rstb.2018.0171.
Covelo-Molares, H., Bartosovic, M., Vanacova S. 2018 RNA methylation in nuclear pre-mRNA processing, WIRES RNA, DOI: 10.1002/wrna.1489
Bartosovic, M; Covelo Molares, H; Gregorova, P; Hrossova, D; Kudla, G; Vanacova S. 2017 N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3′-end processing. Nucleic Acids Res, 45: 11356–11370.
Ustianenko, D; Pasulka J; Feketova, Z; Bednarik, L; Zigackova, D.; Fortova, A; Zavolan, M; Vanacova, S. 2016 TUT-DIS3L2 is a mammalian surveillance pathway for aberrant structured noncoding RNAs. EMBO Journal, 35:2179-2191.

Keywords: mRNA, protein interactions, posttranscriptional RNA modifications

 

2. The role of protein-protein interactions in the dynamics of m6A RNA modification

Supervisor: assoc.prof. Mgr. Štěpánka Vaňáčová, Ph.D.

Annotation:
The internal mRNA modifications play crucial roles in a number of essential processes of eukaryotic organisms. They regulate the production of germ cells, cellular differentiation, response to stress, and defects in this pathway have been linked to a number of human diseases. The aim of this project is to study the protein-protein interactions of factors involved in the regulation of adenosine methylation (m6A) in coding and noncoding RNAs. The student will master number of diverse methodical approaches, such as human cell culture manipulations (cultivation, RNAi, CRISPR/Cas9, etc.), recombinant DNA preparation, protein expression and purification, high-throughput analyses and enzymatic assays.
She/he will have the opportunity to present the results at prestigious international conferences. Moreover, this project will involve collaboration with other leading researches in European institutes.
Prospective student should ideally have done masters in molecular biology/biochemistry and have a laboratory experience in nucleic acids and/or protein purification and analysis. The most highly valued feature will however be excitement for science and strong drive in tackling important biological questions.

Recommended literature:
Rajecka, V., Skalicky, T., Vanacova, S. 2018. The role of RNA adenosine demethylases in the control of gene expression. Biochim Biophys Acta Gene Regul Mech. 1862:343-355. DOI: 10.1016/j.bbagrm.2018.12.001. review
Covelo-Molares, H., Bartosovic, M., Vanacova S. 2018 RNA methylation in nuclear pre-mRNA processing, WIRES RNA, DOI: 10.1002/wrna.1489. review
G. Zheng, J.A. Dahl, Y. Niu, P. Fedorcsak, C.M. Huang, C.J. Li, C.B. Vagbo, Y. Shi, W.L. Wang, S.H. Song, Z. Lu, R.P. Bosmans, Q. Dai, Y.J. Hao, X. Yang, W.M. Zhao, W.M. Tong, X.J. Wang, F. Bogdan, K. Furu, Y. Fu, G. Jia, X. Zhao, J. Liu, H.E. Krokan, A. Klungland, Y.G. Yang, C. He, ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility, Mol Cell, 49 (2013) 18-29. review
Berlivet S, Scutenaire J, Deragon JM, Bousquet-Antonelli C. Readers of the m6A epitranscriptomic code. Biochim Biophys Acta Gene Regul Mech. 2019 Mar;1862(3):329-342. doi: 10.1016/j.bbagrm.2018.12.008. 2019 Jan 17. Review.

Keywords: mRNA, protein interactions, m6A RNA, m6Am, RNA modification