DC 6: Characterization of riboswitch-ligand interactions using NMR spectroscopy and other biophysical methods

PhD project description:

The PhD candidate will conduct RNA preparation suitable for fragment screening for the SAM-I/IV riboswitch using NMR at the Schwalbe group. Complementary fragment screening will be conducted by GCI at Malvern. To guide fragment optimization, a second-site screening at Saverna will be conducted. Further, virtual screening hits and newly synthesized compounds from the ITN consortium will be analysed. For selected ligands, more extensive NMR characterisations will be conducted. Specifically, binding sites will be structurally characterised using isotope-labelled riboswitch samples for resonance assignment as well as NOE-filter experiments. In favourable cases, the structure of the ligand-riboswitch complex will be determined. The NMR focused characterisation will be cross validated by other biophysical technologies including CD spectroscopy and SAXS. In addition, the PhD candidate will contribute to the development of in vitro transcription assays for all riboswitches and the 5’-UTR of ompA using previously established methods to determine the activities of compounds discovered in the ITN consortium.

Research environment:

Within “Structure and Dynamics of Life”, constituting one the Profile Areas of Goethe University, the Center of Biomolecular Magnetic Resonance (BMRZ) is a worldwide leading facility providing cutting-edge instrumentation and methodology. Research in the Schwalbe group contributing to the development of NMR methods to investigate RNA-ligand interaction in solution. Our long-standing expertise in RNA structural biology, biophysics and biochemistry is complemented by a strong network of on-site facilities and institutions. 

Skills/qualifications:

• The applicant should hold a master’s degree or equivalent in chemistry or biochemistry.
• The applicant should be familiar with RNA wet lab work.
• The applicant should be comfortable with the mobility requirements that are part of the attractive program
• 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. organic chemistry synthesis, NMR spectroscopy and NMR data analysis, wet lab molecular biology) 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, Topspin, Sparky (or any related NMR analysis software), Corel Graphics Suite, MS Office is an advantage.
• Good English language skills.

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 chemistry, biochemistry, computational analysis/modelling and structural biology.
• Training program: Access to comprehensive further training program with access to GRADE.
• Scientific collaborations with leading international labs in Germany, Europe and worldwide.
• Mobility: Free public transport in all Hessen (Free State Ticket Hessen)
• Campus: Our attractive campus offers a modern cafeteria, various cafes, and opportunities to rest in numerous green spaces. It is connected to public transport via Bus and Train (U-Bahn lines 3 and 8).
• Professional development: Extensive RNA-centered networks and Mentoring Programmes will benefit your professional development

For more information about the position, please contact Harald Schwalbe.