ORFeus doctoral network
Project 7: Dissecting mechanisms regulating smORF translation from lncRNAs (Julie Aspden)
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The Position
Many lncRNAs, once assumed to be non-coding, in fact carry small open reading frames (smORFs) that ribosomes translate into short proteins, or microproteins, which standard reference catalogs miss. Which lncRNAs are actually translated, and how features of each transcript control the efficiency and location of that translation, remains poorly understood, especially in dynamic processes such as human neuronal differentiation.
This project will uncover the rules that govern lncRNA translation, mapping ribosome scanning with TCP-Seq (translation complex profile sequencing) in human SH-SY5Y neuronal cells and resolving transcript structures with long-read direct-RNA-Seq to pinpoint the regulatory motifs that set translation efficiency. It sits at the regulatory heart of ORFeus Work Package 2, which moves from discovering the dark proteome to understanding its function. The work connects closely to partner projects on single-molecule translation mapping, single-cell validation of candidate regulatory factors, the evolutionary analysis of translation features, and AI-driven prediction of translation.
Main Tasks
- Perform TCP-Seq in human SH-SY5Y neuronal cells to map ribosome scanning and capture 40S and 80S ribosomal subunit dynamics as the cells differentiate into neurons.
- Use long-read direct-RNA-Seq, together with the single-molecule translation mapping of other doctoral candidates (DCs) in the network, here DC2, to identify the transcript features that control ribosome recruitment, and dissect the responsible regulatory factors and motifs using mutational analysis with mini-gene reporters and siRNA knockdowns.
- Validate the top candidate regulatory factors and motifs and combine the results into a comprehensive map of ribosome scanning across lncRNAs.
- Collaborate across the ORFeus network, feeding regulatory-motif data into the prediction models of DC1 and sharing validated multi-ORF transcripts through the ORFeome platform, and produce the project's scientific report.
Methods and Platforms
- Translation complex profile sequencing (TCP-Seq) and ribosome profiling in human SH-SY5Y neuronal cell culture.
- Long-read direct-RNA-Seq (nanopore) to resolve transcript structures and functional dissection with mini-gene reporters and siRNA knockdowns.
- Data analysis, working with consortium datasets via the ORFeome platform.
Secondment
- You will spend around three months at Oxford Nanopore Technologies (Oxford, UK), co-developing novel direct-RNA-Seq-based translation profiling 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.
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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, etc.) in the United Kingdom 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 University of Leeds.
- 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
- An undergraduate or master's degree (or equivalent) in molecular biology, biochemistry, RNA biology, genetics, cell biology, or a related life-science field.
- Hands-on laboratory experience in molecular and RNA biology, for example mammalian cell culture, cloning and reporter assays, or RNA sequencing methods.
- Desirable: experience with translation assays, next-generation or long-read sequencing, basic bioinformatics or scripting (for example R or Python), and an interest in microproteins and the dark proteome.
- Good written and spoken English. The minimum University of Leeds language requirement is IELTS band score 6.0 – with not less than 5.5 in any skill area or Internet based TOEFL 80 (with not less than 17 in listening, 18 in reading, 20 in speaking and 19 in writing). Tests must be taken at a test centre. Conditional offers to successful applicants will provide time to take a test if needed. https://www.leeds.ac.uk/international-admissions/doc/entry-requirements.
- Motivation for interdisciplinary, collaborative research, and willingness to travel for the secondment and network events.
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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 €5,602.04 (£4,481.63) per month, which includes both living allowance and mobility allowance. 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.
- As a member of staff at the University of Leeds you’ll have access to a diverse range of benefits to help support your lifestyle https://jobs.leeds.ac.uk/display.aspx?id=1697&pid=0.
- The MSCA employment contract covers 36 months of full-time, fully funded employment.
Working at the University of Leeds
The University of Leeds is a research-intensive university in the United Kingdom, with strong programs in molecular and cellular biology, RNA biology, and the life sciences. At the University of Leeds, we are committed to providing a culture of inclusion, respect and equity of opportunity that attracts, supports, and retains the best students and staff from all backgrounds and from across the world.
You will join the group of Prof. Julie Aspden, which studies how long non-coding RNAs (lncRNAs) are translated, using ribosome profiling to map translation and its regulation during human neuronal differentiation. You will work closely with the group of Prof. Mar Alba at the Hospital del Mar Research Institute, who brings complementary expertise in the evolution and computational analysis of novel genes and microproteins. You will enroll as a PhD candidate at the University of Leeds Faculty of Health and Life Sciences Graduate School.
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