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Unraveling the molecular basis of immune signaling

Project

Project Details

Program
BioScience
Field of Study
Structural Biology
Division
Biological and Environmental Sciences and Engineering

Project Description

All animals and plants form ‘holobionts’ with a myriad of microorganisms. Accordingly, all organisms have evolved sophisticated immune mechanisms to fight pathogenic microbes, while attracting and nurturing beneficial ones. We use biochemistry, biophysics and structural methods such as X-ray crystallography, small angle X-ray scattering, nuclear magnetic resonance, cryo-electron microscopy and AI-based predictions to reveal the 3D structure of protein complexes involved in controlling the immune system. The student will be embedded in a team of structural biologists and will work on protein production, biophysical and 3D structural analyses. In KAUST we have access to state-of-the art instruments, including last-generation TITAN KRIOS electron microscopes, and high-field NMR; X-ray analysis is performed in France. Prior wet-lab experience would be a plus.

About the Researcher

Stefan Arold
Professor, Bioengineering
Biological and Environmental Science and Engineering Division

Affiliations

Education Profile

  • Habilitation, University of Montpellier, France, 2004
  • Postdoctoral Fellow, University of Oxford, UK, 1998
  • PhD, University of Montpellier, France, 1998
  • MSC, Joseph Fourier University, Grenoble, France, 1994

Research Interests

a€‹Professor Arolda's research interests are focused on integrative structural biology based on hybrid approaches. His work involves inferring structure and function of macromolecular assemblies, to enhance computational methods for functional annotation of genes (system-wide or focused), and to design and engineer molecules with desired properties (switches, genetic/epi-genetic regulators, detectors).

Selected Publications

  • Brami-Cherrier K, Gervasi N., Arsenieva D, Walkiewicz K., Boutterin MC, Ortega A, Leonard PG, Seantier B, Gasmi L, Bouceba T, Noble MEM, Girault JA, Arold ST. (2014) FAK dimerization controls its kinase-dependent functions at focal adhesions. EMBO J. 3,356-370.
  • Suen KM, Lin CC, George R, Melo FA, Biggs, ER, Ahmed Z, Drake MN, Arur S, Arold ST, Ladbury JE (2013) Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli. Nat. Struct. Mol Biol. 20, 620-7
  • Lin C.C., Melo F.A., Ghosh R., Suen K.M, Stagg L.J., Kirkpatrick J., Arold S.T., Ahmed A., Ladbury J.E. (2012) Inhibition of basal FGF receptor signaling by Grb2. Cell, 149, 1514-24
  • Ladbury J.E., Arold S.T. (2012) Noise in cellular signaling pathways: causes and effects. Trends Biochem Sci, 37, 173-8
  • Arold S.T. (2011) How focal adhesion kinase achieves regulation by linking ligand binding, localization and action. Curr Opin Struct Biol. 21, 808-13
  • Declerck N., Bouillaut L., Chaix D., Rugani N., Slamti L., Hoh F., Lereclus D. & Arold S.T. (2007) Structure of PlcR: Insights into virulence regulation and evolution of quorum sensing in Gram-positive bacteria. PNAS, 104, 18490-5

Desired Project Deliverables

The student will be embedded in a team of structural biologists and will work on protein production, biophysical and 3D structural analyses.

Recommended Student Background

wet-lab experience
biochemistry
biophysics
bioimaging