Postdoctoral position Small Molecules that Repartition RNA Conformational Ensembles

University of Groningen via AcademicTransfer; Netherlands; On-site; EUR 52,000 - 68,000; Full time

Benefits offered by this job

End-of-year bonus

Holiday allowance

Job summary

University of Groningen is seeking a postdoctoral researcher for the RNA Structural Dynamics Group at the Groningen Biomolecular Sciences and Biotechnology Institute (GBB).

The project focuses on RNA conformational ensembles and how small molecules reshape them to influence RNA function. You will employ SHAPE/DMS mutational profiling, ensemble deconvolution, and functional assays in cells, with opportunities to supervise PhD/MSc students.

Qualifications

• PhD in Molecular Biology, Biochemistry, Chemical Biology, Biophysics, RNA Biology, Bioinformatics or related field, completed or near completion.
• Hands-on RNA biochemistry or RNA structure probing (SHAPE, DMS, mutational profiling) is a strong asset.
• Experience with small-molecule/RNA interactions, compound screening or biophysical binding assays is desirable.
• Familiarity with sequencing data analysis (Unix/shell, Python, R); RNA structure prediction/ensemble analysis a plus.
• Strong scientific output relative to career stage (publications, conference contributions).
• Enthusiasm for interdisciplinary collaboration and strong written/spoken English.

Responsibilities

• Map how small molecules reshape RNA conformational ensembles using chemical probing and ensemble deconvolution.
• Screen and characterize ensemble-repartitioning compounds.
• Define binding sites and thermodynamic/kinetic basis of repartitioning with chemistry/structural biology partners.
• Link RNA structure to function via reporter assays, translation and splicing readouts.
• Develop methods for high-throughput profiling of RNA structural changes.
• Publish and present findings; supervise PhD and MSc students.

Skills

RNA biochemistry

RNA structure probing

ensemble analysis

computational analysis

english communication

scientific output

Education

PhD in Molecular Biology/Biochemistry

Tools

Unix/shell

Python

R

Job description

Organisation/Company University of Groningen Research Field Biological sciences » Biology Chemistry » Molecular chemistry Chemistry » Biochemistry Researcher Profile Recognised Researcher (R2) Application Deadline 19 Nov 2026 - 23:00 (UTC) Country Netherlands Type of Contract Temporary Job Status Not Applicable Hours Per Week 38.0 Is the job funded through the EU Research Framework Programme? Not funded by a EU programme Is the Job related to staff position within a Research Infrastructure? No

Offer Description

A one-year postdoc position is open in the RNA Structural Dynamics Group at the Groningen Biomolecular Sciences and Biotechnology Institute (GBB).

The appointment will focus on RNA molecules rarely adopt a single structure. Most fold into an ensemble of interconverting conformations, and the balance between these states is often what determines whether an RNA is translated, spliced, degraded or recognised by its partners. RNA has therefore emerged as a major, largely untapped class of drug targets. Yet despite substantial investment, only one small molecule acting on an mRNA (risdiplam) has reached the clinic, and most compounds identified in binding-based screens have no measurable effect on RNA function.

Our recent work suggests why. In a study published in Nature Communications (Zhang et al., 2026), we showed that the FDA-approved anticancer drug mitoxantrone does not simply bind its target RNA: it selectively stabilises one conformation within the RNA’s structural ensemble, repartitioning the population of states and thereby modulating RNA function. Binding to RNA is not enough: changing its shape is what makes a drug work. This points to a different route for RNA-targeted drug discovery, in which compounds are selected not for affinity alone but for their ability to redistribute conformational ensembles in a desired direction.

This project will build on that framework. Combining high-throughput RNA structure probing (SHAPE/DMS mutational profiling), ensemble deconvolution, chemical biology and functional assays in cells, the postdoctoral researcher will establish how small molecules reshape RNA conformational landscapes, identify new ensemble-repartitioning compounds, and define the rules that connect a shift in the structural ensemble to a change in RNA function.

What are you going to do?

As a postdoctoral researcher you will:

• Map how small molecules reshape RNA conformational ensembles using chemical probing (SHAPE/DMS-MaP) of RNA-ligand complexes in vitro and in cells, combined with ensemble deconvolution to resolve individual conformers and quantify ligand-induced repartitioning.
• Screen and characterise ensemble-repartitioning compounds, moving beyond affinity-based readouts to identify molecules that shift the balance between functional and non-functional RNA states on disease-relevant targets.
• Dissect mechanism by defining binding sites, ligand selectivity for individual conformers and the thermodynamic and kinetic basis of ensemble repartitioning, in collaboration with chemistry and structural biology partners.
• Link structure to function through reporter assays, translation and splicing readouts, and transcriptome-wide structure probing to assess on-target effects and selectivity in cells.
• Develop methods and analysis pipelines for the quantitative, high-throughput profiling of ligand- induced changes in RNA structural ensembles, contributing to the lab’s open-source software ecosystem.
• Publish and present your findings in peer-reviewed journals and at international conferences, and contribute to supervising PhD and MSc students in the lab.

We are seeking a curious, focused, and collaborative researcher who thrives on challenges. You will be a strong candidate if you have:

• A PhD in Molecular Biology, Biochemistry, Chemical Biology, Biophysics, RNA Biology, Bioinformatics or a related field, completed or nearly completed.
• Hands-on experience with RNA biochemistry and/or RNA structure probing (e.g. SHAPE, DMS, mutational profiling, next-generation sequencing library preparation) is a strong advantage.
• Experience with small-molecule/RNA interactions, chemical biology, compound screening or biophysical binding assays is highly desirable.
• Familiarity with computational analysis of sequencing data (Unix/shell, Python or R); experience with RNA structure prediction or ensemble analysis is a plus. Candidates with a primarily computational background and a strong interest in experimental validation are also encouraged to apply.
• A strong record of scientific output relative to career stage (publications, conference contributions).
• Enthusiasm for interdisciplinary, collaborative science and willingness to interact closely with chemists and structural biologists within and outside Groningen.
• Good written and spoken English, strong communication, organisational and mentoring skills.

Additional Information

What can you expect from us?

• 232 vacation hours per year, based on a 38-hour workweek (1.0 FTE). You can also work more or fewer hours in exchange for more or fewer free hours. For example, with a 40-hour workweek, you save 96 extra free hours, and with a 36-hour workweek, you lose 96 hours.
• End-of-year bonus of 8.3% and 8% holiday allowance.
• Extensive opportunities for personal and professional development.

Information about applying

When scheduling meetings, we will take your schedule into account as much as possible. The University of Groningen considers social safety important. We strive to be a university where staff and students feel respected and at home, regardless of differences in background, experiences, perspectives, and identity. For more information, see also our page about our diversity policy .

Additional comments

Do you have any questions or need more information?

Questions about the content of the job?
Danny Incarnato (Associate Professor): [e-mail]

Questions about your application process?
Chienes Metus (Managing Coordinator): [e-mail]

Acquisition is not appreciated.