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Accueil du site > Recrutement > Thèses au LPT > Far-from-equilibrium kinetics of DNA zipping and unwinding

Far-from-equilibrium kinetics of DNA zipping and unwinding

par Manoel Manghi - 20 octobre 2015

Toutes les versions de cet article : English , français

PhD advisors : Manoel Manghi & Nicolas Destainville

The double-stranded DNA (dsDNA) double-helix can be unzipped by changing the solution physicochemical conditions (temperature, pH, ionic strength) or by applying forces or torques on it, either mechanically in vitro or with the help of specialized enzymes in vivo. Our group has recently investigated, with the help of original mesoscopic models, how in this context of DNA denaturation, base-pairing degrees of freedom are coupled to the biopolymer dynamics.

In addition to its obvious implication in molecular biology, DNA base-pairing kinetics have recently known a growing interest in nanotechnological applications. It started with polymerase chain reaction (PCR) in the 1980s, more recently followed by aptamer design, DNA biochips, or DNA origami. However, both unwinding from the completely zipped dsDNA to the fully denaturated single-stranded DNAs and the reverse mechanism, called hybridization or zipping, involve complex mechanisms because of the helical character of dsDNA, as illustrated in the Figure below. Indeed, conservation of the molecule linking number Lk, a topological quantity related to the dsDNA helicity, imposes a constraint on the helical twist dynamics. Twist must be evacuated at the unwinding molecule ends in order for the single strands to separate. Conversely, hybridization requires rotation of the molecule for accumulation of twist.

The primary objective of this thesis will be to decipher on analytical grounds how the competition between rotational friction on the single strands and on the double-stranded region dictates the global dynamical laws governing the zipping or unzipping of DNA. The origin of the power laws probably come from the far-from-equilibrium character of the polymers. This issue will first be tackled in the simpler Rouse (free-draining) approximation before being explored by taking hydrodynamic interactions into account.

The theoretical methods used in this Ph.D. work will be analytical and numerical tools, from statistical mechanics (at equilibrium and far from equilibrium) and hydrodynamics. The Ph.D. student will get familiarized with physics applied to biology, which is a very active and topical research area. An effort will be made, as much as possible, on the comparison with experiments.

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Interested candidates must send their complete CV (including the result of Bachelor/Master’s Degree examination or requirement) by email to Manoel Manghi (LPT) and Nicolas Destainville (LPT).

Financial support : not determined