PhD project 1

A new specific knowledge base for modeling and design of RNA-binding proteins

 

Domain: Structural bioinformatics, computational biology, methods development

Key words:  KDD; molecular dynamics; RNA-protein binding energy; protein design

Thesis promotor/supervisor: D. Ritchie / I. Chauvot de Beauchene
Location: LORIA lab (CNRS – INRIA – Lorraine University) at Nancy, France
Starting date: Between March and December 2019
Duration: 36 month
Funding: H2020-MSC-ITN project « RNAct », hold by W. Vranken (VUB, Brussel)
Salary: ~2100 euro/month net (+ family allowance if relevant)

 

Project

The PhD project is part of a multi-disciplinary European ITN project called RNAct (http://rnact.eu/), involving 8 inter-connected PhD projects in computational and experimental molecular biology, biophysics and system biology.
The overarching aim is to design novel RNA recognition motif (RRM) in proteins, for exploitation in synthetic biology and bio-analytics. In this global project, our PhD project focuses on two main axis:

1/ The creation of a complete and comprehensive database of available RRM data : sequence, structure, dynamics, RNA specificity, binding affinity, biological function… This database will help the development of computational approaches in the RNAct project. The PhD student will analyze these different RRM data and will liaise with the other PhD students to enrich the data with results from in silico methodologies.

2/ The computation of protein-RNA binding energies by molecular dynamics simulations of RRM-RNA models. 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.

The PhD student will spend 3 month of secondments at the VUB (Brussel, Belgium) to learn about sequence-based methods for protein design and analysis.

Eligibility

European funding require an international mobility:  The candidates must not have resided or carried out their main activity in France for more than 12 months in the 3 years prior to the recruitment.

Candidates must have a masters degree in any of the relevant disciplines: (bio-)physics, structural biology, bio-informatics or computer science.

The project is highly interdisciplinary: the day-to-day work involves a lot of programming on atomic representations of proteins and nucleic acids. Good programming skills (preferentially Python and/or C++) are essential. Knowledge of structural biology is very desirable, skills in discrete mathematics and statistics would be appreciated. Most importantly, candidates must be motivated to learn about all disciplines relevant to the project.

Candidates must be fluent either in French or in English.

Applications should be sent on the RNAct centralized application web site. On https://wvranken.wufoo.com/forms/zjepab507unqzd/, select project ESR3