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Bioinformatic | Evolution | Structural biology | Molecular mechanisms


Irtelis CEA PhD program

​​​​​​​​​​​​PhD Thesis Proposal​​​

Published on 12 April 2017

​Loc​​ation of the laboratory : CEA Saclay 

TEAM : MOLECULAR ASSEMBLIES AND GENOME INT​​​​EGRITY​​​


TI​TLE : ​

COUPLING NATURAL AND A​​RTIFICIAL COEVOLUTION FOR THE STRUCTURAL PREDICTION OF COMPLEXES​​


Contacts : Jessica ANDREANI (jessica.andreani@cea.f​r) - Raphael GUEROIS  (raphael.guerois@cea.fr) ​
How to app​ly​​ ?​​
KEYWORDS : BIOINFORMATICS , STRUCTURAL BIOLOGY , INTERACTOME , ​​​​DEEP SEQUENCING
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Protein complexes are the working horses of most cellular processes. Our project aims at uncovering how interaction surfaces control the cross-talks between cell machineries with a specific interest for the field of radiobiology and epigenetics [1,2]. Over the past five years, our team developed prediction programs for the structural modelling of protein complexes with the specificity of exploiting evolutionary information [3,4] (InterEvDock server). These methologies were very well ​ranked at the international prediction challenge CAPRI (ranked first for the number of correctly predicted interfaces)[5]. IrtelisPicture.png
The aim of the current PhD project will be to integrate novel type of constraints arising from the "Deep Mutational Scanning" technologies benefiting from the rise of next generation sequencing technologies [6]. These approaches consist in combining the high-throughput generation of protein mutants (>10 of billions) and the screening of these mutants to assess their folding and binding properties. In addition to the information recovered in natural sequence alignments, these methodologies will provide key constraints to increase the precision in intergrative structural modeling. There are a number of computational challenges that remain to be solved in the statistical treatment of the generated data, the accurate and efficient modeling of the mutations effects and in the integration of important détails such as the organisation of the solvent at complex interfaces. The PhD work will involve working on original datasets built or derived in our lab​ which should considerably help increasing the precision of current methods. ​ ​

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Bibliog​​​raphy :
[1] Richet N, Liu D, […], Guerois R, Compper C, Besle A, Guichard B, Almouzni G, Ochsenbein F. Structural insight into how the human helicase subunit MCM2 may act as a histone chaperone together with ASF1 at the replication fork. Nucleic Acids Res. (2015) 43(3):1905-17. 
[2] Jiao Y, Seeger K, Lautrette A, Gaubert A, Mousson F, Guerois R, Mann C, Ochsenbein F. Surprising complexity of the Asf1 histone chaperone-Rad53 kinase interaction. Proc Natl Acad Sci U S A. (2012) 109(8):2866-71. 
[3] Andreani J, Faure G, Guerois R. Versatility and invariance in the evolution of homologous heteromeric interfaces. PLoS Comput Biol. (2012) 8(8):e1002677. 
[4] Andreani J, Faure G, Guerois R. InterEvScore: a novel coarse-grained interface scoring function using a multi-body statistical potential coupled to evolution. Bioinformatics. (2013) 29(14):1742-9. 
[6] Fowler DM, Fields S. Deep mutational scanning: a new style of protein science. Nat Methods. 2014 11(8):801-7. 

University / Graduate School : Université Paris Saclay - ED 569 Innovation thérapeutique du fondamental à l'appliqué ​​​
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Ho​​w to apply ?

  1. Visit ​the Irtelis CEA PhD program Website
  2. Enter the "Application Form" menu (Top-Right)
  3. From there you can fill in your personal data and select the subject "​COUPLING NATURAL AND A​​RTIFICIAL COEVOLUTION FOR THE STRUCTURAL PREDICTION OF COMPLEXES" from the choice list :

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​Don't hesitate to contact us for any question !

Jessica ANDREANI (jessica.andreani@cea.f​r)

​Raphael GUEROIS  (raphael.guerois@cea.fr) ​​