2019-01299 - PhD Position F/M Knowledge-based 3D modeling and design of RNA-binding proteins
Le descriptif de l’offre ci-dessous est en Anglais

Type de contrat : CDD de la fonction publique

Niveau de diplôme exigé : Bac + 5 ou équivalent

Fonction : Doctorant

Contexte et atouts du poste

Thesis promotor/supervisor: M.-D. Devignes / I. Chauvot de Beauchene
Location: LORIA lab (CNRS – INRIA – Lorraine University) at Nancy, France
Starting date: Between June 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)

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.

RNAct research aim is the design of novel proteins containing RNA recognition motifs (RRM), for exploitation in synthetic biology and bio-analytics. This is achieved through a design cycle that starts with computational approaches at the sequence and structure levels of proteins and RNA, in order to select amino acid positions and mutations for large-scale phage display experiments with RNA screening. Viable RRMs will be further investigated at the atomic level with integrative structural biology approaches, and will be applied in synthetic biology, to post-transcriptionally regulate fatty acid processing via RRMs, and in bio-analytics, to detect RNA in-cell and design RNA biochips.

The CAPSID research group develops computational tools for data mining on macromolecular assemblies and 3D modeling of those assemblies. We are part of an informatics-mathematics lab (LORIA), and have several collaborations with experimental biology/biophysics teams.

The PhD student will work in collaboration with another PhD from the RNAct project (working on protein-RNA docking) and a Post-Doc working on the representation of protein flexibility in docking.

Mission confiée

Our PhD project focuses on two main axis:

1/ The creation of a complete and comprehensive database of available RRM information from the many available databases. This includes their sequence, structure, dynamics, RNA specificity and other data (binding affinity, biological function...). This database will be regularly extended with internal and external data as it becomes available, will be published and released at the end of the project as a deliverable, 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. The database will serve for application of machine learning to sequence-to-structure predictions and design

2/ The computation of protein-RNA binding energies by molecular dynamics simulations of RRM-RNA 3D models. For example, we will first investigate why the Drosophilia Sex-lethal (Sxl) protein, and its putative human homologue HuR, bind more specific RNA sequences than the U2AF65 protein. Then, we will predict the RNA-binding specificities of the newly designed proteins.

Principales activités

The PhD student will work in collaboration with another PhD from the RNAct project (working on protein-RNA docking) and a Post-Doc working on the representation of protein flexibility in docking.

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.

Compétences

Candidates must have a masters degree in bio-informatics or computer science.

The project is highly interdisciplinary. Good programming skills (preferentially Python and/or C++) are essential. Skills in database creation and managment, knowledge-based discovery, machin learning and/or statistics are very desirable. Knowledge of structural biology would be appreciated (but not mendatory).

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.

Avantages

  • Subsidized meals
  • Partial reimbursement of public transport costs
  • Leave: 7 weeks of annual leave + 10 extra days off due to RTT (statutory reduction in working hours) + possibility of exceptional leave (sick children, moving home, etc.)
  • Possibility of teleworking (after 6 months of employment) and flexible organization of working hours
  • Professional equipment available (videoconferencing, loan of computer equipment, etc.)
  • Social, cultural and sports events and activities
  • Access to vocational training
  • Social security coverage

Rémunération

Salary: 1982€ gross/month for 1st and 2nd year. 2085€ gross/month for 3rd year.

Monthly salary after taxes : around 1596,05€ for 1st and 2nd year. 1678,99€ for 3rd year. (medical insurance included).