At the Department of Biochemistry (University of Zürich) we have an immediate opening for a PhD student working in the field of protein engineering and structural biology. The successful candidate will joint a multidisciplinary team of scientists from combinatorial biochemistry and protein engineering (Prof. A. Plückthun), molecular dynamics (Prof. A. Caflisch), NMR spectroscopy (Prof. O. Zerbe) and X-ray crystallography (PD P. Mittl). It is the goal of this joined project to develop a toolbox of peptide recognition modules (on the basis of the Armadillo repeat) which can be assembled on a rational basis to recognize any extended peptide with a given sequence. Several scaffolds of binding modules have already been developed but it will be the goal of this PhD thesis to design and synthesize artificial Armadillo-repeat proteins that can be crystallized with the cognate polypeptides. Experience (at the master-level) in structure-based planning of mutants, general molecular biology tools, protein expression and purification is mandatory and knowledge of protein X-ray crystallography would be an asset. The project will involve mutant design and structure determination by X-ray crystallography. For further information, please consult the following publications or send an e-mail to either mi...@bioc.uzh.ch or plueckt...@bioc.uzh.ch.

Designed Armadillo repeat proteins: library generation, characterization and selection of peptide binders with high specificity. Varadamsetty G, Tremmel D, Hansen S, Parmeggiani F, Plückthun A.J Mol Biol. 2012; 424:68-87

Optimization of designed armadillo repeat proteins by molecular dynamics simulations and NMR spectroscopy. Alfarano P, Varadamsetty G, Ewald C, Parmeggiani F, Pellarin R, Zerbe O, Plückthun A, Caflisch A. Protein Sci. 2012; 21:1298-314

Structure-based optimization of designed Armadillo-repeat proteins. Madhurantakam C, Varadamsetty G, Grütter MG, Plückthun A, Mittl PR. Protein Sci. 2012;21:1015-28

Designed armadillo repeat proteins as general peptide-binding scaffolds: consensus design and computational optimization of the hydrophobic core. Parmeggiani F, Pellarin R, Larsen AP, Varadamsetty G, Stumpp MT, Zerbe O, Caflisch A, Plückthun A.J Mol Biol. 2008 ;376:1282-304

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