DC 5: Targeting RNA to reshape the gut microbiome

PhD project description:

The aim of the project within the consortium is to study microbiota changes upon administration of compounds active against riboswitches and novel small molecules developed in other project parts in the consortium. In a first step, existing riboswitch active compounds, e.g. for the FMN riboswitch (the non-natural ligands roseoflavin or ribocil) will be tested in vivo in the complex and bacterially diverse microbiome to set a proof of concept that modulation of the gut microbiome by riboswitch modulators is feasible. To do so, the 16S rDNA-sequencing based pipeline to study the microbiome will be complemented by establishing shotgun metagenomics sequencing in a microbiome mouse model. In a second step, an indicator E. coli strain will be utilized and spiked into the microbiome by faecal microbiota transfer to test on target-activity of FMN riboswitch modulators. In a last step, the antibiotic activity of novel riboswitch modulators as single agents and in combination derived from other project parts within the consortium will be tested in vivo to elucidate their impact on the microbiota composition and determine their in vivo activity. Additionally, general toxicity measurements as well as immune profiling is planned to closely monitor side effects.

Research environment:

The Department of Hematology / Oncology of the University Hospital Frankfurt offers a broad diagnostic and therapeutic spectrum for patients with solid tumors and malignant diseases of the hematopoietic system. The research group led by Dr. Sebastian Scheich is dedicated to investigating the crosstalk between the microbiome and disease outcomes, particularly cancer, in preclinical rodent models and clinical patient samples. The research team itself is embedded in the excellent research infrastructure of the University Hospital in Frankfurt, the Frankfurt Cancer Institute and the DKTK partner site Frankfurt. Moreover, the department and works closely with the Institute for Medical Microbiology and Hospital Hygiene and Department of Infectious Diseases.

Skills/qualifications:

• The applicant should hold a master’s degree or equivalent in biology, biochemistry, molecular medicine or related fields.
• Comfort to work with rodent models.
• A high level of motivation, flexibility and responsibility as well as very good communication skills in German or English are expected.
• Expertise in experimental techniques (e.g. high throughput sequencing analyses, mouse models, FACS analysis) is an advantage.
• Motivation to learn, apply and establish new techniques, ability to critically analyze and reflect data.
• Good skills with the following programs python, R, Adobe Illustrator, MS Office is an advantage.
• Good English language skills.
• Due to legal regulations, valid proof of measles immunity / measles vaccination is required.

Benefits/salary/social security:

• Collective agreement: In addition to an attractive salary based on a collective agreement, with an annual special payment, you benefit from long-term security through company pension schemes. This collective agreement is 3342 € living allowance and 600 € mobility allowanc, acording to the MSCA work programme.
• Attractive working environment: We offer you an interesting, versatile and attractive working environment in a highly motivated, international team consisting of MDs and PhDs with background in basic science, immunology, computational analysis/modeling and translational cancer research.
• Training program: Access to comprehensive further training program with access to DKTK School of Oncology and Mildred-Scheel Network.
• Scientific collaborations with leading international labs in the US and in Europe.
• Mobility: Free public transport in all Hessen (Free State Ticket Hessen).
• Campus: Our attractive university hospital campus offers a modern cafeteria, various cafes, and opportunities to rest in numerous green spaces. A walk on the riverside of the Main offers relaxation during breaks.
• Work-Life-Balance: Employment according to the MSCA rules, we offer childcare in our daycare center (if you have any questions, please contact Ms. Häfner at 069 / 6301 83863), childcare during holidays).
• Health Promotion: Benefit from our attractive health offers. We offer regular online and face-to-face courses on nutrition, relaxation, sports and exercise.
• Professional development: Internal and external training for your professional development.

For more information about the position, please contact Sebastian Scheich.