|CCL 18.09.26 Paris Pasteur University International Doctoral Program. Targeting G proteins by cancer-promoting immunomodulatory virulence factors.|
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Date: Wed Sep 26 17:34:10 2018
Subject: 18.09.26 Paris Pasteur University International Doctoral Program. Targeting G proteins by cancer-promoting immunomodulatory virulence factors.
The Cytotoxic Necrotizing Factor 1 (CNF1) from pathogenic Escherichia coli catalyzes a post-translational modification (PTM) of Rho family members through site-specific deamidation of a glutamine residue into a glutamic acid which places Rho in a constitutively active state. We propose to define by Structural Bioinformatics approaches combined with Cell Biology and Biochemistry approaches the molecular basis of the modification by CNF1 of the subfamily of Rho GTPases that belong to the super-family of p21-Ras GTPases. This integrated study will open new avenues for a comprehensive view of several hot topics in the field. The first aspect concerns the potential connection of pathogens to cancer development. The second aspect is the role played by the disordered or partially disordered protein regions in the cell signalisation processes. The PhD project intends to use molecular modeling approaches coupled to experimental approaches to explore: (A) the interactions between CNF1 and small G proteins to shade light on the specificity of recognition of Rho proteins by this toxin. Starting from a model proposed for CNF1/RhoA interaction, molecular dynamics trajectories will be recorded to analyze the interaction between CNF1 and other small G proteins. Model prediction and CNF1 activity will be confronted by directed mutagenesis of the toxin and analysis of its activity in vitro and in cellulo. (B) the possibilities to inhibit the interaction of CNF toxins with their host targets. A virtual screening study will be performed on series of conformations extracted from extensive MD trajectories. The predicted inhibitors will be experimentally tested.
The Institut Pasteur in Paris organizes a doctoral program in collaboration with the universities Paris-Descartes, Paris-Diderot, Pierre and Marie Curie, and Paris-Sud, for students holding a master degree or the equivalent in science, medicine and related fields delivered by a university outside of France. In 2009, the Institut Pasteur, the world leading biomedical research institute founded by Louis Pasteur in 1887, inaugurated the Pasteur Paris-University (PPU) international doctoral program in collaboration with several major Parisian science universities for students holding a Master degree (or equivalent) from a university outside of France and who have not worked or resided in France for more than 12 months in the 3 years prior to their recruitment. The 2018-2019 call for enrollment of students in October 2019 is open until November 2nd, 2018. Please go to the dedicated platform: https://ppu.pasteur.fr where you can find the project described (OncoVirF project) and to submit your application. Deadline for contacting host laboratories: November 2, 2018 Deadline for submitting the application with the host laboratory: November 13, 2018 Interview week: January 29 / February 1, 2019 Contact: therese.malliavin^^pasteur.frNOTE THAT E-MAIL ADDRESSES HAVE BEEN MODIFIED!!!
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