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Synthetic biology of RNA

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Our team develops a set of methods to engineer RNA systems with gene regulatory functions : “RNA switches”. On the one hand we develop numerical tools for designing RNA sequences using computer simulations of the dynamical folding of RNA, on the other hand we implement genetically the designed RNA switches and we test and characterize their gene regulatory function in vitro and in vivo in bacteria.

Context
RNA molecules plays a fundamental role in numerous cellular processes. Similarly as for proteins, the functions and mechanisms of action of RNA molecules depend critically on their ability to efficiently fold into complex dynamical structures. Hence, the information contained in an RNA sequence ‘encodes’ not only its final structure but also its folding paths, that is the set of transient intermediate folding states that efficiently guide the RNA molecule towards its final functional structure.

Scientific project
To develop an effective synthetic biology of RNA, we have adopted an original learning-by-designing approach : we design functional RNA sequences while incorporating the sequence-folding-function relationship in RNA. This approach allows us to investigate the principles for encoding folding paths in an RNA sequence.
On the one hand we develop numerical tools based on computer simulations of the dynamical folding of RNA to design RNA sequences with genetic regulatory functions : "RNA switches". On the other hand, we test and characterize experimentally those designed RNA switches : we implement them genetically, we test them in vitro, then we use them in vivo to control gene expression in bacteria.

Goal of the internship
The student will be involved in the experimental aspect of the project and will be trained if necessary on the various techniques used. The aim of the internship will be to achieve one or several of the following goals :

  • genetic implementation (cloning) of RNA switches already designed in the laboratory,
  • functional characterization of those new switches in vitro (by in vitro transcription and quantitative analysis on gels),
  • functional characterization of the switches in vivo in bacteria (Northern blots and fluorescence measurements in microplates).

Contact
LIPhy laboratory (UGA/CNRS, Grenoble) : https://www-liphy.ujf-grenoble.fr
BIOP Team
Alexandre Dawid – alexandre.dawid@univ-grenoble-alpes.fr – tél. : 04 76 51 47 65