DC 8: Mode of action studies

PhD project description:

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 used. 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 UiB.

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 (GUF 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 fecal microbiota transplants in vivo will be developed based on the existing reporter gene assays allowing the monitoring of RNA ligands in a microbiome model (secondment GUF).

The candidate is expected to co-supervise MSc-students and participate actively in professional activities within the TargetRNA network, the research group and the Department of Biotechnology. 

Research environment:

Matthias Mack is the head of the Institute for Technical Microbiology at MUAS and studies the physiology of microorganisms, the workhorses of classical and modern biotechnology. We employ a wide range of molecular biology and biochemical techniques to discover and examine genes and enzymes of primary and secondary metabolism in aerobic bacteria. Furthermore, we study expression of these genes and the corresponding control elements such as riboswitches. We are particularly interested in the metabolism of vitamins and the effect of antivitamins such as the antibiotic roseoflavin from the bacterium Streptomyces davaonensis and related species. Roseoflavin is one of the few known drugs that interact directly with FMN riboswitches after cytoplasmic activation. Incidentally, just last year we isolated a novel bacterial species, Streptomyces berlinensis, that also produces roseoflavin.

The PhD position is associated to the Mack research group at the Institute for Technical Microbiology in the department of biotechnology: Dr. Mack - Institut für Technische Mikrobiologie (hs-mannheim.de)

Skills/qualifications:

• 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.

Personal and relational qualities will be emphasized. Ambitions and potential will also count when evaluating the candidates.

Benefits/salary/social security:

• A good and professionally stimulating working environment.
• Salary as PhD research fellow (100%) in the state of Baden-Württemberg (Germany) salary scale (EG 13 TV-L). This constitutes a gross annual salary of € 54.700 to 61.600. Further increases in salary are made according to length of service in the position.
• The benefits of the public service on the basis of the TV-L, such as a company pension scheme, capital-forming benefits and an annual special payment
• Company health management measures
• Working in a convenient location with excellent VRN and DB connections
• The employment relationship is limited to 3 years (start 01.01.2025). The position is, in principle, divisible.
• In order to increase the proportion of female employees, qualified women are expressly encouraged to apply.
• Severely disabled applicants (f/m/d) will be given priority if they are suitable.

For more information about the position, please contact Matthias Mack.