Structure Determination By X-Ray Crystallography Of An Engineered Yeast 80s Ribosome Provides New Understanding On Macrolides Binding In Eukaryotes
Reference : PhD Gulnara Yusupova
Publication de l'offre : 24 janvier 2018
Our group is interested since many years in the understanding of mechanism of binding and molecular implications of small molecule inhibitors to the ribosome during protein synthesis. Particularly exciting and promising results have been recently published by our labs concerning inhibitors with promising anticancer properties bound to the eukaryotic 80S ribosome. To continue and further enlarge our vision about this topic, we are collaborating with several groups which have engineered the eukaryotic 80S ribosome and shown that it is more sensitive to macrolides, a particular class of inhibitors known already to target bacterial ribosome, but not the eukaryotic one.
The aim of proposed project to crystallize and determine the structures of the engineered 80S ribosome alone and in the complex with several different macrolides. Accurate model building will allow to observe the molecular interactions that occur between the inhibitors and the ribosome and will be essential to develop new derivatives with increased potential, especially towards the wild-type ribosome. This, in turn, will have a tremendous impact in the cancer field, since it will likely contribute with a novel promising class of compound with antitumor properties.
We believe that this project will be very well suitable for a PhD candidate since preliminary results are already available in our lab and since we have a long-term knowledge about yeast 80S ribosome purification and crystallization. It will be a highly enriching topic of research and provide the candidate with extensive experience in ribosome structural biology and mechanism of inhibition of protein synthesis.
Date limite de candidature : 1 novembre 2018