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"POSITION: We have a Postdoctoral position available immediately and until December 2019, with the possibility of extension for a further year. We are looking for motivated candidates with a background in molecular genetics and/or peptide biochemistry. The project will use cutting edge methods (CRISPR, RiboSeq, Punch-P) to reveal the function of key smORFs in Drosophila and zebrafish, aiming to test our model for smORF classification and function (see below).
BACKGROUND: Small open-reading frames (smORFs or sORFs) of 100 codons or less are usually excluded from proteome annotations. However, the metazoan genomes, including humans, contain thousands to millions of smORFs, that we have shown can have key biological functions (Pueyo 2016, PloS Biology 14: e1002395; Magny 2013 Science 341:1116). We showed that Drosophila melanogaster contains thousands of smORFs actively translated, often in lncRNAs, producing peptides of mostly unknown function (Aspden 2014 eLife 3: e03528). We propose the existence of smORF classes, from cis-regulators of translation, to expression of functional peptides with a propensity to act as regulators of membrane-associated proteins, or as components of ancient protein complexes in the cytoplasm (Couso and Patraquim 2017 Nat.Rev.Mol.Cell Biol.18:575). We also propose that different smORF classes represent steps during the evolution of novel peptides and proteins from non-coding sequences.