TranSplice
ERC Starting Grant project (2025-2029)
Kinetoplastids are a family of flagellate protists that includes numerous parasitic species responsible for serious human diseases such as sleeping sickness, Chagas disease, and leishmaniasis. These unicellular eukaryotes have a unique cellular and molecular biology that differs from that of the majority of other organisms, making their study both fascinating and essential for combating the diseases they cause.
With TranSplice, we aim to the study an essential yet little understood molecular mechanism: SL trans-splicing. This process enables kinetoplastids to generate their messenger RNAs (mRNAs) from long polycistronic precursors by adding a small RNA molecule, the 'Spliced Leader' (SL), to the 5' end of each mRNA via a unique machinery called the trans-spliceosome. Although this machinery is essential for gene expression, the lack of structural information and the high divergence of its RNA and protein elements have hindered a mechanistic understanding of how kinetoplastids employ SL trans-splicing to generate their entire mRNA transcriptome.

Our methodology
Using a combination of genome editing, high-resolution cryo-electron microscopy, AI-based interactome analyses, and in vivo assays, we investigate the SL snRNP biogenesis and the central mechanism of trans-splicing orchestrated by the highly divergent kinetoplastid trans-spliceosome.
Our Team
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