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Structural Studies Of Candida Albicans Ribosome By X-Ray Crystallography

Reference : PhD Marat YUSUPOV

Offer publication : April 6, 2016

Our laboratory is studying the structure and function of the ribosomes from several organisms. Ribosome is a large ribonucleoprotein complex with a molecular weight that varies from 2.3 MDa in bacteria to 4.3 MDa in higher eukaryotes. While controlling the mRNA/tRNA interaction and catalyzing the peptide bond formation, it is responsible for protein synthesis and as such is one prop of all cellular operation. The ribosome is thus
considered as the favored target for drugs.

Although the 3D structures at atomic resolution of ribosomes originating from several prokaryotic and eukaryotic organisms have recently been obtained, none from pathogens are available. Candida albicans is one of the most affective fungi in hospitals. In particular, it occurs in patients highly susceptible to systemic infections after being exposed to intense chemical treatments (AIDS, cancers and bacterial infections). Moreover, the apparition of a large number of resistant strains results in the need for further developments of new antifungal treatments. Sadly, no antifungal drug specifically directed against C. albicans has been developed.

Solving the 3D structure of the ribosome from C. albicans will unravel at atomic resolution why ribosome from C. albicans is not inhibited by most commonly used antifungal and will allow development of new drugs based on these observations.
We plan to conduct data measurements at SOLEIL synchrotron on the beamlines PROXIMA 1 and 2A, to which we have access on a regular basis. We are already able to grow C. albicans ribosome crystals suitable for x-ray data collection at third generation synchrotrons. Currently, we could obtain medium range resolution datasets (4.7 Å) displaying a monoclinic space group P21, with two ribosomes per asymmetric unit. Solving the 3D structure of the ribosome from C. albicans will assist in applying specific and selective drug screenings in view of developing molecules with no side effects for the host.

- COMPETENCES SOUHAITEES : Le candidat devra avoir de solides bases théoriques et pratiques en biochimie et biologie moléculaire.

- EXPERTISES QUI SERONT ACQUISES AU COURS DE LA FORMATION : Production, caractérisation et cristallisation du ribosome eucaryote à
partir de cultures de Candida albicans. Collecte, affinement et analyse des données de diffraction. Modélisation moléculaire.

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