Ruprecht-Karls-Universität Heidelberg
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Jaeschke0119 - Scientist (f/m) / PhD position
Project no:
Jaeschke0119

Project leader:

Project supervisor:
Jäschke, Andres
Application deadline:
31. May 2019
Start of PhD project:
1. Jul 2019

Project description:

Title:
Evolutionary origin of the genetic code
Summary:
The Jäschke lab has recently become a member of the DFG-funded Collaborative Research Center 235 “Emergence of Life – exploring mechanisms with cross-disciplinary experiments” (www.emergence-of-life.de). In 16 projects, (bio-, theoretical) physicists, (bio-, geo-, astro-) chemists, and biologists tackle questions ranging from the first synthesis of organic matter in space via RNA-world scenarios to the evolution of cells and metabolism. Our group is testing – in a joint project with the group of Prof. Dieter Braun (LMU Munich) – different hypotheses on how the first systems for a coded peptide synthesis may have evolved. This field is rich in hypotheses and speculation, sequence data correlation and modeling, but largely devoid of real (wet-lab) experiments. This is going to change in this project. While the Braun group focusses on binding affinities, the Jäschke group will deal with reactivities of specifically designed RNA libraries with aminoacyl adenylates in order to experimentally test various hypothetical scenarios and prebiotic conditions. This project builds on our core expertise of interfacing chemistry and molecular biology with modern next-generation sequencing (NGS) technology to answer previously inaccessible questions [1-3].
Here, we will use NGS as a tool to extract rate constants for about 20.000 RNA library members from a single (bio)chemical experiment (remotely similar to [4]). Briefly, the RNA library is incubated with an activated amino acid, and after different reaction times the aminoacylated fraction is isolated and analyzed by Illumina sequencing. Read numbers can be converted into concentrations, and concentrations measured at different time points yield reaction rates. Therefore, the NGS data need to be analyzed using existing bioinformatics tools and to-be-developed custom scripts.
Once this methodology is in place, we will use it to test different hypotheses regarding the origin of the genetic code, such as the relationships between “anticodon” sequences and the preferentially charged amino acids, the preference of L-amino acids over D-amino acids, or the role of “helper” peptides as primoridial aminoacyl tRNA synthases. Thus, the project will consist of ~10% chemistry, 50% biochemical lab experiments, and 40% bioinformatics.
References:
[1] Ameta, S., Winz, M.-L., Previti, C. & Jäschke, A.: Next-generation sequencing reveals how RNA catalysts evolve from random space. Nucleic Acids Res. 2014 (42), 1303-10.

[2] 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.

[3] 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.

[4] Jalali-Yazdi, F., Lai, L.H., Takahashi, T.T., Roberts, R.W.: High-througput measurement of binding kinetics by mRNA display and next-generation sequencing. Angew. Chem. Int. Ed. 2016, 55, 4007-10.
Methods that will be used:
the project will consist of ~10% chemistry, 50% biochemical lab experiments, and 40% bioinformatics.
Cooperation partners:
Prof. Dr. Dieter Braun, systems biophysics, LMU Munich.
The collaborative nature of the project will involve regular travel to Munich.
Personal qualifications:
Applicants should be primarily molecular biotechnologists or biochemists who have:
- Good hands-on experience in standard molecular biology techniques; prior experience with RNA is a bonus.
- Experience in the analysis of NGS data.
- Familiarity with python (preferred) or R.
- Some exposure to synthetic chemistry.
The successful candidate will be part of an interdisciplinary team of Postdocs, PhD students, Master students and technicians. A special incentive will be membership in the collaborative research center 235 “Emergence of Life – exploring mechanisms with cross-disciplinary experiments” (www.emergence-of-life.de) and its graduate program.
Keywords:
Origin of life, coded peptide synthesis