Ruprecht-Karls-Universität Heidelberg
HBIGS homepage | Forgot password
Dieterich0119 - Scientist (f/m) / PhD position
Project no:
Dieterich0119

Project leader:

Project supervisor:
Dieterich, Christoph
Application deadline:
15. Sep 2019
Start of PhD project:
1. Oct 2019

Project description:

Title:
Circular RNAs: novel markers and regulators of cardiac myocyte cell fate
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 mouse, rat, pig and human 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 rat cell lines together with our collaborators. As a next step, we will use circular RNAs to open up novel therapeutic avenues based on animal models of heart disease.

The selected applicant will 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.

Secondly, (2) the applicant will enhance our work on effective tools to knock-down or over-express circular RNAs of interest. This may also include computationally designed circular RNAs with specific functional characteristics in mind.

References:
Jakobi T, Uvarovskii A, Dieterich C. circtools - a one-stop software solution
for circular RNA research. Bioinformatics. 2018 Nov 21. doi:
10.1093/bioinformatics/bty948.

Siede D, Rapti K, Gorska AA, Katus HA, Altmüller J, Boeckel JN, Meder B, Maack
C, Völkers M, Müller OJ, Backs J, Dieterich C. Identification of circular RNAs
with host gene-independent expression in human model systems for cardiac
differentiation and disease. J Mol Cell Cardiol. 2017 Aug;109:48-56. doi:
10.1016/j.yjmcc.2017.06.015.

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.

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 / Biochemistry
• Cloning, qt-PCR
• High-throughput sequencing technologies
• Metabolic labelling
• Sub-cellular fractionation
• Affinity purification techniques (RNA and protein baits)
• Knock-down and over-expression (AAV system)
• Cell Culture (NRVMs, hiPSC cells)
Cooperation partners:
Prof. Johannes Backs, University Heidelberg, Germany.
Personal qualifications:
Candidates should possess a Master’s Degree or equivalent qualification in biophysics, biochemistry, molecular biology, 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, cardiomyocyte, circular RNA, Computational Biology, bioinformatics, Cardiovascular diseases