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In collaboration with Olivier Rivoire at CIRB (College de France Paris), we are seeking a candidate for a 2-year postdoc position:

Postdoctoral position: statistical protein evolution

Two-year position to work with Clément Nizak and Olivier Rivoire in Paris.

Scientific context:

Proteins recapitulate at a molecular scale much of our difficulty to develop a theory of living matter: we know precisely what constitutes a protein (a sequence of amino acids) but we lack a simple framework to understand how the many ”functions” that proteins perform (specific binding, catalysis, information transmission…) emerge from the interactions between their constituents.

Nature built proteins through the dynamical process of evolution by natural selection and our approach is to study the relation between protein sequence and function via this process. To this end, we combine analyses of natural protein sequences, experiments of molecular evolution and mathematical models based on statistical physics.

Experimentally, our current workflow consists in constructing libraries of millions of mutants of an enzyme, which we encapsulate one by one in mono-disperse droplets. The proteins in each droplet are expressed, assayed for enzymatic function using fluorescent assays and sorted into bins that correspond to each level of enzymatic activity. High-throughput sequencing of genes that encode the proteins in each bin yields quantitative information on the relation between sequence (genotype) and function (phenotype).

We propose to apply this workflow to develop a general strategy of sequence space exploration, which will be applied to the evolution of proteins towards new function and to the design of new functional proteins.

Location:

Our new lab is located in the Center for Interdisciplinary Research in Biology at Collège de France in the heart of Paris (https://www.college-de-france.fr/site/en-cirb/). We exchange and collaborate with colleagues in nearby institutions including ESPCI (A, Griffiths, P. Nghe, Y. Rondelez), Ecole Normale Supérieure (R. Monasson, S. Cocco, D. Laage), IBPC (F. Sterpone, G. Stirnemann) and Université Pierre et Marie Curie (M. Weigt), as well as international collaborators at UT Southwestern in Dallas (R. Ranganathan, W. Russ) and Politecnico di Torino (A. Pagnani).

Expected profile: 

We are looking for candidates motivated by this interdisciplinary approach to protein evolution, with experience in molecular biology and, preferably, a background in physics, mathematics or computer science. The position is available immediately for a period of two years.

References:

S. Boyer, D. Biswas, A. K. Soshee, N. Scaramozzino, C. Nizak, O. Rivoire (2016). Hierarchy and extremes in selections from pools of randomized proteins. PNAS 113, 3482.

O. Rivoire, K. Reynolds, R. Ranganathan (2016). Evolution-based functional decomposition of proteins. PLoS Comput Biol 12:e1004817.

A. Fallah-Araghi, J.-C. Baret, M. Ryckelynck, A.D. Griffiths (2012). A completely in vitro ultrahigh-throughput droplet-based microfluidic screening system for protein engineering and directed evolution. Lab Chip 12, 882.

Web pages : 

O. Rivoire: http://evophysics.net

C. Nizak: https://blog.espci.fr/nizak/

Contacts:

Olivier Rivoire, CIRB, Collège de France, Paris –  olivier.rivoire AT college-de-france.fr

Clément Nizak, LBC, ESPCI, Paris – clement.nizak AT espci.fr

Laboratory of Biochemistry ESPCI ParisTech – CNRS