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Directed evolution by dual selection

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Date : 08/09/2011

Internship proposal for : Master 1 or Master 2

Laboratory
Laboratoire Interdisciplinaire de Physique
UMR5588 CNRS & Université Grenoble 1
140 av. de la Physique
38402 Saint Martin d'Hères
Website : http://www-liphy.ujf-grenoble.fr/-BIOP-?lang=en
Main discipline : Synthetic Biology
Lab director : Jacques Derouard

Mentor
Alexandre Dawid
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tél : +33 4 76 51 47 65

Subjects
1.: Synthetic biology
2.: RNA switches

Tools and methodologies
1.: Molecular biology
2.: Microbiology
3.: Computational design

Summary of lab's interests

Our research aims at exploiting the versatility of RNA molecules to design tailor-made RNA regulators as components in synthetic biology approaches. Using dynamic simulations of RNA folding, we work at determining design principles of such systems and at developing related computational and experimental approaches.

Summary of project

Directed evolution techniques make use of natural evolution mechanisms (diversification/selection cycles) in order to create or optimize a desired function. In the case of regulatory mechanisms, the selected "function" is somewhat sophisticated in the sense that the associated phenotype is not unique but dependents on regulatory factors. In such a case, a special selection method (said "dual") has to be used in order to take account of the alternative expected outcomes. Furthermore, the selection can rely either on the detection of a reporter gene which is then used to sort the variants, or on "natural" selection where the survival of variants is conditioned to the expression of the desired phenotype. This second method, which doesn't rely on the individual assessment of the variants, is more subtle but also more powerful. We propose to work on the implementation of such a method for the RNA regulatory systems we are developing.