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Chaque projet soutenu par Gebert Rüf Stiftung est présenté sur le site web de la fondation avec en particulier les données de base du projet. Par cette publication, la fondation informe sur les résultats du soutien accordé et contribue à la communication scientifique au sein de la société.

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Membrane yeast two-hybrid technology and drug discovery

Rédaction

Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.

Coopération

Diese Rubrik wird erst seit 2010 erfasst.

Données de projet

  • Numéro du projet: GRS-011/04 
  • Subside accordé: CHF 334'000 
  • Consentement: 02.07.2004 
  • Durée: 09.2004 - 10.2007 
  • Champs d'activité:  Pilotprojekte, 1998 - 2018

Direction du projet

Description du projet

The parasite pasmodium falciparum causes the most severe form of human malaria with over 2 Mio. deaths per year. The project aims at developing an in vivo gentetic approach in yeast to characterize plasmodium falciparum proteins with their particular human transmembrane receptor in order to develop a yeast-based drug discovery assay.
The project will extend the application of the modified Membrane Yeast Two-Hybrid (MYTH) technology to identify a receptor/ligand interaction from any model organism and will establish the MYTH as a tool for drug discovery. The novel approach is effective since it’s unconventional, cheap (uses yeast as model organism) and fast (yeast is amenable to high-throughput applications).

Quelles sont les particularités de ce projet?

The financial support of Gebert Rüf Stiftung will be used as an initial finance for this applied and interdisciplinary project with a possible commercial application. It is unique since the MYTH technology (patented in the research group) is the only technology that can be used to detect interactions between membrane proteins using a screening format in vivo.

Etat/résultats intermédiaires

We constructed a new plasmid vectors for expression of Plasmodium falciparum EBA-175 peptide ligand and human glycophorin A receptor in yeast. In addition, we successfully expressed the human glycophorin A receptor in the yeast plasma membrane and reconstituted the EBA-175/glcophorin A interaction using the modified MYTH system. We are currently setting up of the “reverse MYTH“ system to screen and identify compounds of therapeutical value that inhibit the EBA-175 ligand/glycophorin A receptor interaction.
Furthermore, we used a novel version of MYTH technology (called iMYTH) to identify six novel interactors of the yeast ABC transporter Ycf1p, a yeast homolog of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which, when disabled by mutation, causes cystic fibrosis, a hereditary disease that results in progressive disability and early death. These newly discovered protein interactors represent novel potential pharmaceutical targets. Through a series of biochemical and genetic tests, we discovered that one of these interactors, Tus1p, regulates Ycf1p transporter function in a completely novel way to stimulate its ability to remove toxins from the cell.

Publications

Revue de presse

Liens

Dernière mise à jour de cette présentation du projet  21.12.2018