Micropeptides as a new class of bio-active peptides in higher eukaryotes.

01 January 2014 → 31 December 2019
Research Foundation - Flanders (FWO)
Research disciplines
  • Engineering and technology
    • Other engineering and technology
Project description

Micropeptides are a type of non--‐classical bio--‐active peptides, translated from short open reading frames (sORFs; <100 amino acids). Due to the lack of an N--‐terminal signaling peptide signature, they are immediately set free in the cytoplasm after translation. Recently, such peptides were discovered in several eukaryotic organisms and more interestingly the biological function of one of them, the tarsal--‐ less gene micropeptide, was revealed in Drosophila melanogaster. It plays a role in early development by regulating epidermal differentiation. In mammals this type of bio--‐active peptides is yet to be discovered, but several assumptions strengthen the idea that these are also present in higher eukaryotes. The objective is to discover new micropeptides in Drosophila melanogaster and Mus musculus. This project combines both wet--‐lab and theoretical (in silico) experiments. Ribosome profiling experiments (recently described NGS--‐based technique to sequence ribosome--‐captured mRNA fragments) will elucidate the translated mRNA of both model organisms. Furthermore different MS--‐based peptidomics strategies will be performed attempting to confirm the discovery of the micropeptides from the aforementioned NGS experiment. In parallel, a peptide prediction algorithm will be devised based on known and new micropeptide sequence characteristics and their conservation. Finally, the discovered micropeptides will be tested for activity on a panel of different cell lines. Integration of the aforementioned experiments will undoubtedly lead to discovery of new micropeptides, in the same way as microRNA, an important but long time overlooked class of bio--‐active molecules.