Ruprecht-Karls-Universität Heidelberg
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Jaeschke0120 - Scientist (f/m) / PhD position
Project no:
Jaeschke0120

Project leader:

Project supervisor:
Jäschke, Andres
Application deadline:
15. Jul 2020
Start of PhD project:
1. Oct 2020

Project description:

Title:
Coenzyme- and metabolite-linked RNAs as a new paradigm in epitranscriptomics
Summary:
The research group of Prof. Dr. Andres Jäschke at the Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, offers 3-year PhD positions funded by a recently awarded ERC Advanced Grant. The candidates will study novel epitranscriptomic mechanisms of gene regulation by combining techniques of biochemistry, molecular biology and bioinformatics.
Background:
The Jäschke group is among the leading labs in epitranscriptomics, studying the role of natural RNA modifications in biology. By discovering and characterizing regulatory RNAs connected to the redox coenzyme NAD in various bacteria [1-3] we contributed to the establishment of a new field, directly linking redox biology and gene expression. We also reported the first enzyme that can remove this novel RNA modification [4]. Recently, Prof. Jäschke was awarded an Advanced Grant by the European Research Council, providing generous funding for the next five years, starting in October 2020.
Objectives:
NAD is just one of many coenzymes and metabolic intermediates that share certain structural features. The aim of this project is to establish the scope and biological significance of coenzyme-linked RNAs in biology. We will expand our NAD captureSeq protocol to include reduced, phosphorylated, deamidated, and depyridinated NAD-RNAs. We will develop new capture methods to identify cellular RNAs modified with coenzyme A, flavin, thiamine, and N-acetylglucosamine. We will apply these protocols to RNAs isolated from different organisms to explore the occurrence, abundance, and structural variety of such RNAs. For selected modified RNAs, we will unravel the biological significance and biosynthesis.
Further information can be found at jaschkelab.de.
References:
[1] Cahová, H., Winz, M.-L., Höfer, K., Nübel, K. & Jäschke, A.: NAD captureSeq indicates NAD as a bacterial cap for a subset of regulatory RNAs. Nature 2015 (519) 374-7.

[2] Winz, M.-L., Cahová, H., Nübel, G., Frindert, J., Höfer, K., Jäschke, A.: NAD captureSeq – capturing and sequencing NAD-capped RNA sequences. Nat. Protocols 2017 (12) 122-49.

[3] Frindert, J., Zhang, Y., Nübel, G., Kahloon, M., Kolmar, L., Hotz-Wagenblatt, A., Burhenne, J., Haefeli, W.E. & Jäschke, A.: Identification, biosynthesis and decapping of NAD-capped RNAs in B. subtilis. Cell Rep. 2018, 24, 1890-1901.

[4] Höfer, K., Li, S., Abele, F., Frindert, J., Schlotthauer, J., Grawenhoff, J., Du, J., Patel, D.J. & Jäschke, A.: Structure and function of the bacterial decapping enzyme NudC. Nat. Chem. Biol. 2016 (12) 730-4.
Methods that will be used:
Our team combines approaches from various fields, including genetics, biochemistry, chemistry, and mass spectrometry to define the functions and mechanisms of gene regulation by coenzyme-linked RNAs. Within this interdisciplinary project the PhD candidate will learn, develop, and apply state-of-the-art techniques ranging from transcriptome-wide profiling to detailed mechanistic studies.
Cooperation partners:
various
Personal qualifications:
We are looking for enthusiastic and motivated candidates who have a strong interest in RNA bio-chemistry and who would like to challenge textbook wisdom. The applicants should hold a Master’s degree in molecular biology, biochemistry, biotechnology or a related discipline and should have demonstrated academic excellence in their studies. Initiative, creativity, team spirit, excellent English language skills and a solid background in molecular biology are essential traits. Practi¬cal experience in RNA biology, next-generation sequencing, and/or mass spectrometry is a bonus.
Keywords:
Epitranscriptomics, RNA biology, RNA modification, RNA biochemistry