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RiboStruct : a new spin-off from IGBMC

From left to right: Marat Yusupov, Gulnara Yusupova and Jean-Paul Renaud

Nov. 5, 2015

One year after the publication in Nature of 16 crystallographic structures of the yeast 80S ribosome in complex with various inhibitors by the teams of Marat Yusupov and Gulnara Yusupova, the RiboStruct start-up project led by Jean-Paul Renaud has now materialized.

After publishing in 2010 the crystallographic structure of the full yeast ribosome, the teams of Marat and Gulnara have been constantly perfecting their techniques and acquired undeniable expertise for the crystallization of the eukaryotic ribosome and the study of its function. Today the resolution with which they are able to observe this structure is sufficiently precise to allow the design of new drugs targeting the eukaryotic ribosome. Potential targets are the ribosome of pathogenic yeasts such as Candida or unicellular parasites such as Plasmodium, Trypanosoma or Leishmania, but the main objective is to target the human ribosome for the treatment of genetic disorders caused by nonsense mutations.

 

Already creator in 2002 of AliX (merged in 2009 with Novalyst Discovery to give birth to NovAliX), Jean-Paul Renaud has an entrepreneurial spirit. Former IGBMC researcher on detachment, he has long followed the results of Marat and Gulnara’s teams, and he finally joined them late 2014 to create a start-up leveraging their expertise. After a maturation phase (2013-2014) funded by Conectus and carried by Nicolas Garreau de Loubresse after his PhD thesis in the laboratory of Marat, the RiboStruct project was laureate in 2014 of the French national Innovation Contest in the "emergence" category. The RiboStruct company, co-founded by Marat, Gula, Nicolas (currently post-doc at the Wyss Institute in Harvard) and Jean-Paul, has been created in October 2015. Jean-Paul, again on secondment from CNRS, is its CEO.

 

Treating genetic disorders caused by nonsense mutations
Nonsense mutations are point mutations inducing the replacement of a codon encoding an amino acid by a stop codon. This type of mutation leads to the synthesis of a truncated protein, often non-functional. Some compounds, such as certain aminoglycosides, upon binding to the decoding site, allow to "pass through" premature stop codons. This mechanism called readthrough restores the synthesis of a full-length protein albeit with a mutated residue, which generally does not affect the overall function. In favorable cases, the synthesis of a few % of the full-length protein provides a therapeutic benefit.
Having solved the crystallographic structure of the yeast 80S ribosome in complex with an aminoglycoside, researchers are now trying to design more potent and less toxic analogs. RiboStruct just signed a first fee-for-service contract on bacterial ribosome to start the activity, and is trying to raise funds to finance its eukaryotic ribosome R&D project.

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