PhD Project "Mode of action studies: in vivo characterization of highly specialized RNAs - bacterial riboswitches" (Mack 3105) - Heidelberg University

Employer

Institute for Technical Microbiology, Mannheim University of Applied Sciences, Mannheim, Germany

Description

The biotechnology department at Mannheim University of Applied Sciences (MUAS) is looking for a PhD candidate (full position acccording to TV-L E13, 100%) for the in vivo characterization of highly specialized genetic elements, bacterial riboswitches.
RNA is an essential biomolecular polymer that exhibits many cellular functions that are crucial for life, ranging from catalytic to informational. The recently discovered versatile cellular functions of RNA have rendered RNA an interesting target for therapy. In particular, the prospect of targeting RNA with small molecule modulators offers great promise for tackling currently challenging diseases. Traditional drug molecules have mainly been designed to target proteins. In the Marie Sklodowska-Curie Doctoral Training network “TargetRNA” we will develop selective drugs that target RNA instead.
As a PhD candidate, you will work on the development of new methods to study RNA targeting. This PhD position will be part of a large European consortium focusing on developing drug molecules that target RNA. In this particular position, the focus will be on the in vivo characterization of highly specialized RNAs, bacterial riboswitches.

The PhD project will focus on the in vivo characterization of highly specialized genetic elements, bacterial riboswitches. To monitor the biological activity of various riboswitch ligands in cellulo reporter gene assays (employing different bacterial hosts) will be employed. Suitable genetic elements must be assembled in plasmid vectors and coupled to a dual luciferase-based test system. The assays will be employed to investigate whether (novel) RNA ligands indeed interfere with gene expression in a dynamic riboswitch system. The experiments will be complemented by SPR studies at University of Bergen (Norway). Further, the antimicrobial activities of the compounds from other working packages will be tested on different target microorganisms (E. faecalis, E. faecium, S. salvarius, S. anginosus, B. faecis, B. vulgatus, A. baumannii, E. coli, C. albicans, off-target: B. obeum, F. prausnitzii, E. limosum) which will be challenged with different levels and combinations of hit compounds and possible antimicrobials. For the most promising ligands, resistant mutants will be studied in greater detail. Whole genome sequence analysis of these resistors will validate the mode of action of the hit compounds (University of Frankfurt, Germany, secondment). Sequence analysis employing state-of-the-art data science tools will help us to study possible off-target effects of the hit compounds. If needed to rationalize the data, we will measure compound uptake into target cells using mass spectrometry. Finally, an indicator E. coli strain for faecal microbiota transplants in vivo will be developed based on the existing reporter gene assays allowing the monitoring of RNA ligands in a microbiome model (University of Frankfurt, Germany, secondment).

Candidate requirements

• Applicants must hold a master's degree or equivalent education in microbiology, molecular biology, biochemistry or biotechnology. Master students can apply provided they complete their final master exam before starting the project. It is a condition of employment that the master's degree has been awarded.
• Applicants must have a documented solid background in microbiology and molecular biology.
• Mastery of state-of-the-art cloning techniques (e.g. classical techniques, Gibson assembly) is a prerequisite.
• Experience with bioinformatics and data science is an advantage.
• Applicants must be able to work independently and in a structured manner and demonstrate good collaborative skills.
• Applicants must be proficient in both written and oral English.
• We seek a person interested in antimicrobial compounds. Since we use a variety of molecular biology tools, the candidate must have practical experience regarding DNA and RNA molecules and molecular cloning. The candidate should moreover have solid knowledge in bacterial physiology and biochemistry. A master’s degree in microbiology, biochemistry, biotechnology, molecular biology or related fields is a prerequisite.

Further details

Please read more under "Open PhD Positions" on: https://www.hbigs.uni-heidelberg.de/

Possible start of employment: Wednesday, 01 January 2025.

Contract: Full-time, Fixed-term

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