The position

Standard reference catalogs describe only a fraction of what the genome actually translates. Many small open reading frames (smORFs), short stretches of RNA that can be translated into microproteins, sit outside those catalogs, and some may be produced together from a single polycistronic transcript, an RNA that carries more than one protein-coding region. Which ORF a ribosome translates can also depend on the exact RNA isoform, the particular spliced version of a transcript, and conventional methods struggle to link a given translation event to the specific isoform it came from.

This project maps translation at single-molecule resolution and connects it to individual transcript isoforms. It uses approaches such as RiboSTAMP, in which an RNA-editing enzyme is fused to a ribosomal protein so that translating ribosomes leave a chemical mark on the RNA they read. Paired with long-read sequencing platforms such as Oxford Nanopore direct RNA sequencing, full-length transcripts and how they are translated can be read one molecule at a time. Within ORFeus Work Package 1, DC2 is the transcript-level detection arm: it supplies high-resolution, isoform-level experimental data that grounds the computational predictions built across the network, and it connects to partner projects on AI-based smORF prediction, rare translation events, RNA modification effects on translation, and single-cell translation.

Main tasks

● Build multi-omics computational methods that combine RiboSTAMP data with other translation modalities (ribosome profiling (Ribo-seq), polysome profiling, etc) to map translation onto specific RNA isoforms. Quantify how features such as RNA structure and RNA modifications such as m6A influence translation, based on suitable RNA foundation models. Here we will draw on models, data and expertise from the projects of other doctoral candidates (DCs) in the network, particularly DC1 and DC7.

● Contribute to validating the ongoing implementation of RiboSTAMP in the lab, under normal conditions and perturbations (stress), to arrive at stable estimates of differential translation.

● Test whether RiboSTAMP can be run at single-cell resolution and generate isoform-level estimates of translation level and variance, for integration with DC1 AI predictions, DC3 rare-event catalogs, and DC9 single-cell validation.

● Collaborate across the ORFeus network, share validated protocols and isoform-level datasets via the ORFeome platform, and produce the project's scientific report.

Methods and platforms: bioinformatics and genomics; machine learning and deep learning for genomics; RNA structure and modifications; single-molecule direct sequencing and ribosome profiling (Ribo-seq) data analysis; working with public and consortium datasets and models via the ORFeome platform and HuggingFace.

Secondment: you will spend around three months at Oxford Nanopore Technologies (Oxford, UK), developing and optimizing nanopore-based direct RNA sequencing and analysis workflows for RiboSTAMP applications. You will also be guided by an independent academic advisor, with the possibility of a short, primarily virtual research exchange to strengthen the project.

Your profile

MSCA eligibility

You must meet all of the following on your recruitment date:

● You do not already hold a doctoral degree. If you have defended a doctoral thesis but the degree has not yet been formally awarded, you are not eligible.

● Mobility rule: you must not have lived or carried out your main activity (work, studies, and so on) in Germany for more than 12 months in the 36 months immediately before your recruitment date. Compulsory national service, short stays such as holidays, and time spent in a procedure to obtain refugee status under the Geneva Convention do not count toward the 12 months.

● You hold, or will hold before the start date, a degree that formally entitles you to enroll in a doctorate, and you can enroll in the doctoral program at the Max Delbrück Center / Humboldt-Universität zu Berlin.

Candidates of any nationality may apply. There is no limit on prior research experience, as long as you do not already hold a doctorate.

Project-specific profile

● A master's degree (or equivalent) in bioinformatics, computational biology, data science or computer science, or a quantitative degree with comparable experience in analysing and modeling data from the life sciences.

● Hands-on experience with omics data analysis and/or applied machine learning.

● Desirable: experience with next-generation sequencing (including nanopore or other long-read sequencing), and an interest in RNA based gene regulation including microproteins and the dark proteome.

● Excellent written and spoken English.

● Motivation for interdisciplinary, collaborative research, and willingness to travel for the secondment and network events.

What we offer

A full-time employment contract for 36 months as a salaried researcher, with full social security coverage, under the rules of the Marie Skłodowska-Curie Actions. This is a paid employment contract, not a stipend or scholarship.

The indicative gross salary for this position is 62,500 EUR in the first year and 67,300 EUR in the following years. This is what you are paid before income tax and your own social-security contributions are deducted.

Beyond salary, you will receive:

● Supervision by a world-leading, interdisciplinary supervisory team.

● A secondment of around three months with an ORFeus industry partner (Oxford Nanopore Technologies).

● A structured training program: network-wide schools, transferable-skills training, workshops, and international conferences.

● Enrollment in a doctoral program leading to a PhD.

Working at Max Delbrück Center

The Max Delbrück Centre for Molecular Medicine, part of the Helmholtz Association, aims to transform the medicine of tomorrow through our discoveries today. Our researchers draw on interdisciplinary collaboration to unravel the complexity of diseases at the systems level – from molecules and cells right through to organs and the entire organism. Through academic, clinical and industrial partnerships, as well as global networks, we strive to translate biological discoveries into applications that enable the early detection of health abnormalities, personalise treatment and ultimately prevent diseases. Founded in 1992, the Max Delbrück Centre today inspires and supports a diverse pool of 1,800 talented individuals from over 70 countries.

You will join the group of Prof. Uwe Ohler at the MDC site in Berlin-Mitte, which develops machine learning and experimental approaches for studying RNA regulation and translation, including ribosome profiling analysis and the detection of non-canonical open reading frames. You will work closely with the group of Prof. Eivind Valen at the University of Oslo, who brings complementary bioinformatics and ribosome-profiling expertise, including the large-scale analysis of translation across public ribo-seq datasets. You will enroll as a PhD candidate at Humboldt-Universität zu Berlin, the degree-awarding partner of the Max Delbrück Center, and be a full member of MDC’s graduate school with access to its programs.