Knowledge-based modeling and design of RNA-binding proteins

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<div>&nbsp;</div><div><u>Kewords</u>: KDD, molecular dynamics simulation, RNA-protein binding energy, Protein design</div><div><u>Domain</u>: Structural bioinformatics, Computational biology, Methods development</div><div>&nbsp;</div><div><strong>Context</strong></div><div>&nbsp;</div><div>The PhD project is part of a multi-disciplinary European ITN project called RNAct, involving 8 inter-connected PhD projects in computational and experimental molecular biology, biophysics and system biology.</div><div>&nbsp;</div><div>The overarching aim of RNAct is to integrate experiment and computation to design novel RNA recognition motif (RRM) proteins for exploitation in synthetic biology and bio-analytics. RNAct will create and characterize novel functional RRMs with customized recognition of specific single-stranded RNA (ssRNA). Our approach requires novel computational methodology for representing and designing RRMs that can handle the dynamic nature of ssRNA and of particular RRM regions involved in binding, such as flexible linkers. The computational design, combined with high-throughput phage display experiments, aims to deliver RRMs for proof-of-concept applications in synthetic biology and bio-analytics.</div><div>&nbsp;</div><div><strong>Project</strong></div><div>&nbsp;</div><div>In this global project, our PhD project focuses on two main axis:</div><div>&nbsp;</div><div>1/ The creation of a complete and comprehensive database of available RRM information from the many available RRM data covering a broad range of behaviours (with initial help of the other PhD students in the project). This includes their sequence, structure, dynamics, RNA specificity and other data (binding affinity, biological function&hellip;). This database will be regularly extended with internal and external data as it becomes available, will be released at the end of the project, and is key to the development of computational approaches in the RNAct project. The PhD student will analyse these different RRM data, and will liaise with the other PhD students to enrich the data with results from in silico methodologies.</div><div>&nbsp;</div><div>2/ The computation of protein-RNA binding energies by molecular dynamics simulations of RRM-RNA models obtained by his/her fellow- PhD students. For example, he/she will investigate why the Drosophilia Sex-lethal (Sxl) protein, and its putative human homologue HuR, bind more specific Py-tracts than the U2AF65 protein and cannot accommodate cytosine.</div><div>&nbsp;</div><div>Read more here:</div><div></div><d… PhD student will spend 3 month of secondments at the VUB (Brussel, Belgium) to learn about sequence-based methods for protein design and analysis.</div><div>&nbsp;</div><div><strong>Eligibility / Requirements</strong></div><div>&nbsp;</div><div>European funding require an international mobility:&nbsp; The candidates<strong> must not have resided or carried out their main activity in France for more than 12 months </strong>in the 3 years prior to the recruitment.</div><div>&nbsp;</div><div>Candidates must have a masters degree in any of the relevant disciplines: (bio-)physics, structural biology, bio-informatics or computer science.</div><div>&nbsp;</div><div>The project is highly interdisciplinary: the day-to-day work involves a lot of programming on atomic representations of proteins and nucleic acids. Good scripting and programming skills (Python, bash) are essential. Knowledge of structural bioinformatics is very desirable, skills in data-base management and in KDD are highly desirable. Most importantly, candidates must be motivated to learn about all disciplines relevant to the project.</div><div>&nbsp;</div><div>Candidates must be fluent either in French or in English.</div><div>&nbsp;</div><div><strong>Applications</strong> should be sent on the RNAct centralized application web site (ESR3 project):</div><div>&nbsp;</div><div>&nbsp;</div><div>&…;
Laboratoire: LORIA (CNRS - INRIA - UL)