Project Dissecting mechanisms regulating smORF translation from lncRNAs; Julie Aspden

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.

• 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.

• 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 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…