The position

Only a small part of the genome is annotated as protein-coding, yet genetic variants that fall outside these annotated regions can still change how nearby sequences are translated. How such variants alter regulatory translation, including where and how efficiently ribosomes begin translation, remains poorly understood, and interpreting non-coding genetic variation is an open problem at the interface of genetics and dark proteome research.

This project will adapt Ribosome Decision Graphs (RDGs) for genotype specificity, combining public resources (UK Biobank, gnomAD) with publicly available (RiboSeq.Org) and newly generated DepMap ribosome-profiling data to map how genetic variants affect translation initiation, reinitiation, and leaky scanning, and to identify cancer-relevant translation-altering SNPs. It sits within ORFeus Work Package 3, which investigates the roles of the uncharacterised proteome in cancer and immunology.

Main tasks

● Adapt Ribosome Decision Graphs (RDGs) for genotype specificity, drawing on public data (UK Biobank, gnomAD, RiboSeq.Org) and newly generated DepMap ribosome-profiling data, and integrate isoform-level translation data from the project of another doctoral candidate (DC) in the network, here DC2.

● Map how genetic variants affect translation initiation, reinitiation, and leaky scanning, and work with DC3 to build an integrated map of translation diversity that links variant-triggered and naturally rare translation events.

● Identify a set of cancer-relevant translation-altering SNPs and advance tools for interpreting non-coding variants in patient-derived datasets, sharing DepMap data with DC8 for evolutionary analysis and informing DC13's work on codon substitutions.

● Collaborate across the ORFeus network, contribute datasets and analytical tools to the shared platform, and produce the project's scientific report.

Methods and platforms: ribosome profiling (Ribo-seq) generation and analysis, including techniques such as TCP-seq, Ribosome Decision Graph (RDG) modeling adapted for genotype specificity; long-read RNA-seq for identifying cancer-specific isoforms; and analysis of human genetic variation using public resources (UK Biobank, gnomAD) and DepMap data, working through the RiboSeq.Org platform.

Secondment: you will spend around three months at Immagina Biotechnology (Trento, Italy), quantifying variant-driven translation changes using the company's translation measurement technologies. 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 Ireland 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 University College Cork.

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, genetics, computer science, data science, or a related quantitative or life-science field with strong computational skills.

● Strong programming skills (for example Python or R) and hands-on experience working with large genomic or sequencing datasets.

● Desirable: experience with ribosome profiling or RNA-seq data, human genetic variation data (for example variant calling or population-genomics resources such as gnomAD), and an interest in improving fundamental understanding of genomic information.

● Good 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 salary has a living allowance and a mobility allowance, plus a family allowance if you have family obligations when you are recruited. The indicative gross salary for this position is €50,008 p.a. It includes mobility allowances and family allowances (applicable only to researchers with family obligations). This is €4,167.34 per month. 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 (Immagina Biotechnology).

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

● Enrollment in a doctoral program leading to a PhD.

The MSCA employment contract covers 36 months of full-time, fully funded employment. In line with the host institution's doctoral policy, the host funds completion of the doctorate beyond the 36-month MSCA contract as continued employment at the standard national doctoral salary scale; terms confirmed at offer stage.

Working at the University College Cork

University College Cork (UCC) is a research-intensive university in Ireland, with strengths in bioinformatics, computational biology, and the biological sciences. UCC hosts a popular suite of data and computational resources for Ribosome Profiling Data Analysis under the umbrella of RiboSeq.Org. Several Schools (e.g. Biochemistry and Pharmacy) have several faculties with strong expertise in RNA Biology and development of RNA therapeutics.

You will join the group of Prof. Pasha Baranov, which develops computational methods for analyzing ribosome profiling data and modeling translation, including the Ribosome Decision Graph (RDG) framework that this project builds on. You will work closely with the group of Prof. Alexander van Oudenaarden at the Hubrecht Institute, who brings complementary expertise in single-cell analysis and translation dynamics. You will enroll as a PhD candidate at University College Cork Biochemistry Programme.

Project 12: Impact of genetic variation in regulatory translons on protein expression (Pasha Baranov)

Benefits

Job Description