Ruprecht-Karls-Universität Heidelberg
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Dieterich0117 - Scientist (f/m) / PhD position
Project no:
Dieterich0117

Project leader:

Project supervisor:
Dieterich, Christoph
Application deadline:
30. Sep 2017
Start of PhD project:
1. Nov 2017

Project description:

Title:
Circular RNAs: novel regulators of protein synthesis in neurons and cardiac myocytes
Summary:
Circular RNAs are a rediscovered class of RNA species that originate from back-splicing events in animals and plants. Many circular RNAs are stable, abundant and conserved between species. They exhibit context-dependent expression patterns, which are linked to disease states. Putative circular RNA functions are numerous and range from regulation of transcription and splicing to RNA/protein sponging and scaffolding.

We have carefully mapped the complete internal structure of many circular RNAs in adult mouse brains and hearts with innovative RNA sequencing and software approaches. Based on the primary sequence and contextual splicing events, we classified circular RNAs into functional candidate categories, such as mRNA traps, splicing regulators, and sponges.

The Dieterich Lab wants to accurately understand, manipulate and design circular RNA biology in terms of functional aspects. We will predominantly use in vitro cell culture systems of human and mouse cell lines together with our collaborators. Given success, we will use circular RNAs to open up novel therapeutic avenues in animal models of neuronal disease & heart failure.

Given previous experience, the applicant will either work on:

(1) Enhancing our understanding of circular RNA biogenesis, modification, localization, decay and interactions in an unbiased manner using latest high-throughput technologies combined with metabolic labeling, sub-cellular fractionation, and affinity capture experiments.

Alternatively, (2) the applicant will work in quantitative computational models to predict circular RNA dynamics, folding and, interaction networks with the goal to tailor molecular interventions in the heart.

Start: 1 Sep 2017 or later.
References:
Siede et al., Identification of circular RNAs with host gene-independent ex-pression in human model systems for cardiac differentiation and disease, JMCC, accepted.

Metge, F.; Czaja-Hasse, L. F.; Reinhardt, R. & Dieterich, C. (2017), 'FUCHS-towards full circular RNA characterization using RNAseq.', PeerJ 5, e2934.

Malone, B.; Atanassov, I.; Aeschimann, F.; Li, X.; Grosshans, H. & Dieterich, C. (2017), 'Bayesian prediction of RNA translation from ribosome profiling.', Nucleic acids research.

Piechotta, M.; Wyler, E.; Ohler, U.; Landthaler, M. & Dieterich, C. (2017), 'JACUSA: site-specific identification of RNA editing events from replicate sequencing data.', BMC bioinformatics 18, 7.

Jakobi, T.; Czaja-Hasse, L. F.; Reinhardt, R. & Dieterich, C. (2016), 'Profiling and Validation of the Circular RNA Repertoire in Adult Murine Hearts.', Genomics, proteomics & bioinformatics 14, China, 216-23.

Cheng, J.; Metge, F. & Dieterich, C. (2016), 'Specific identification and quantification of circular RNAs from sequencing data.', Bioinformatics (Oxford, England) 32, 1094-6.

Please also visit our web site: https://www.dieterichlab.org
Methods that will be used:
Molecular RNA Biology
• High-throughput sequencing technologies
• Metabolic labelling
• Sub-cellular fractionation
• Knock-down

Computational RNA Biology:
• R Programming
• Python Programing
Cooperation partners:
Prof. Gerhard Schratt, ETH Zurich, Switzerland.
Prof. Johannes Backs, University Heidelberg, Germany.
Personal qualifications:
Candidates should possess a Master’s Degree or equivalent qualification in biophysics, biochemistry, bioinformatics, or a related discipline. Candidates should preferably have a good background in statistics, experience in scripting/programming, possess excellent communication skills, and have a genuine interest in interdisciplinary research.
Keywords:
hiPSC, neuron, cardiomyocyte, circular RNA, Computational Biology, bioinformatics, heart failure, neuronal diseases