Dorota Kostrz

Godfroid — 2019-10-10T12:53:20Z

Abstract

The residence time of a drug on its target has been suggested as a more pertinent metric of therapeutic efficacy than the traditionally used affinity constant. Here, we introduce junctured-DNA tweezers as a generic platform that enables real-time observation, at the single-molecule level, of biomolecular interactions. This tool corresponds to a double-strand DNA scaffold that can be nanomanipulated and on which proteins of interest can be engrafted thanks to widely used genetic tagging strategies. Thus, junctured-DNA tweezers allow a straightforward and robust access to single-molecule force spectroscopy in drug discovery, and more generally in biophysics. Proof-of-principle experiments are provided for the rapamycin-mediated association between FKBP12 and FRB, a system relevant in both medicine and chemical biology. Individual interactions were monitored under a range of applied forces and temperatures, yielding after analysis the characteristic features of the energy profile along the dissociation landscape.

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CNRS press release

Nat Nanotechnol. 2019 Sep 23. doi : 10.1038/s41565-019-0542-7

Odile MALIET

Godfroid — 2019-06-20T16:40:06Z

Abstract

Understanding how and why diversification rates vary through time and space and across species groups is key to understanding the emergence of today's biodiversity. Phylogenetic approaches aimed at identifying variations in diversification rates during the evolutionary history of clades have focused on exceptional shifts subtending evolutionary radiations. While such shifts have undoubtedly affected the history of life, identifying smaller but more frequent changes is important as well. We developed ClaDS—a new Bayesian approach for estimating branch-specific diversification rates on a phylogeny that relies on a model with changes in diversification rates at each speciation event. We show, using Monte Carlo simulations, that the approach performs well at inferring both small and large changes in diversification. Applying our approach to bird phylogenies covering the entire avian radiation, we find that diversification rates are remarkably heterogeneous within evolutionarily restricted species groups. Some groups such as Accipitridae (hawks and allies) cover almost the full range of speciation rates found across the entire bird radiation. As much as 76% of the variation in branch-specific rates across this radiation is due to intraclade variation, suggesting that a large part of the variation in diversification rates is due to many small, rather than few large, shifts.

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Nat Ecol Evol. 2019 Jun 3. doi : 10.1038/s41559-019-0908-0.

ENS - MemoLife

Dorota Kostrz

Abstract

Odile MALIET

Abstract