Dissecting mechanisms regulating smORF translation from lncRNAs

Applications are open from 1 October to 22 October 2026 and must be submitted through the official ORFeus website:<br /> https://orfeus-dn.eu/apply<br /> The recruitment follows a centralised procedure. Applicants will first be checked for eligibility under the MSCA mobility and other requirements. Eligible candidates are then asked to:<br /> <br /> Select up to three projects (out of 15 available) that match their interests. Candidates will be considered for every project they select, so we encourage applicants to explore the full list and choose broadly.<br />

<p><strong>PhD project</strong><br /> 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.<br /> 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.</p> <p>Main tasks:<br /> ●    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.<br /> ●    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.<br /> ●    Validate the top candidate regulatory factors and motifs and combine the results into a comprehensive map of ribosome scanning across lncRNAs.<br /> ●    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.<br />  </p> <p><strong>Methods and platforms: </strong><br /> 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.</p> <p><strong>Secondment: </strong><br /> 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.</p> <p><strong>ORFeus doctoral network opens recruitment: </strong></p> <p>15 PhD positions to decode the 'dark proteome'<br /> The ORFeus doctoral network, a new Marie Skłodowska-Curie Actions Doctoral Network (MSCA-DN) funded by the European Union's Horizon Europe programme, is now recruiting 15 PhD candidates. The network brings together 14 leading research institutions and 12 industry partners across twelve countries to study the dark proteome: a group of small proteins (microproteins) whose existence was unknown until recently. These proteins regulate key processes in cells, including cancer cells, and may hold the key to entirely new treatments, such as immunotherapy. University of Leeds is proud to be part of this ambitious programme.<br />  </p> <p><strong>A rapidly emerging field</strong><br /> Research into the dark proteome is developing fast. Thanks to recent discoveries, including thousands of previously unknown proteins identified through work published in Nature, scientists are beginning to understand how microproteins influence disease. The ORFeus network aims to train a new generation of researchers who will build the tools and methodologies to turn these insights into clinical applications, potentially leading to new targets for cancer therapy and beyond.<br />  </p>

<p>Applications are open from 1 October to 22 October 2026 and must be submitted through the official ORFeus website:<br /> <a href="https://www.orfeus-dn.eu/apply/">https://orfeus-dn.eu/apply</a><br /> The recruitment follows a centralised procedure. Applicants will first be checked for eligibility under the MSCA mobility and other requirements. Eligible candidates are then asked to:</p> <p>Select up to three projects (out of 15 available) that match their interests. Candidates will be considered for every project they select, so we encourage applicants to explore the full list and choose broadly.<br />  </p> <p>For detailed eligibility please refer to: <a href="https://www.orfeus-dn.eu/about/">https://www.orfeus-dn.eu/about/ </a></p> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

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