Catégorie d'actualités : PASTEUR

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

Extensive efforts have been devoted to develop new substrates for culture and differentiation of human induced pluripotent stem cells (hiPSCs) toward cardiac cell-based assays. A more exciting prospect is the construction of cardiac tissue for robust drug screening and cardiac tissue repairing. Here, we developed a patch method by electrospinning and crosslinking of monolayer gelatin nanofibers on a honeycomb frame made of poly(ethylene glycol) diacrylate (PEGDA). The monolayer of the nanofibrous structure can support cells with minimal exogenous contact and a maximal efficiency of cell–medium exchange whereas a single hiPSC colony can be uniformly formed in each of the honeycomb compartments. By modulating the treatment time of the ROCK inhibitor Y-27632, the shape of the hiPSC colony could be controlled from a flat layer to a hemisphere. Afterwards, the induction and differentiation of hiPSCs were achieved on the same patch, leading to a uniform cardiac layer with homogeneous contraction. This cardiac layer could then be used for extracellular recording with a commercial multi-electrode array, showing representative field potential waveforms of matured cardiac tissues with appropriate drug responses.

N’hésitez pas à consulter le communiqué de presse relatif à cet article : Des cellules souches pour reconstruire un coeur !

References:
Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers
Yadong Tang, Li Liu, Junjun Li, Leqian Yu, Li Wang, Jian Shi and Yong Chen
Nanoscale, 2016, 8, 14530-14540
DOI : 10.1039/C6NR04545F

Alessandro Volta Medal

Christian Amatore was awarded by the Alessandro Volta Medal of the Electrochemical Society (ECS). He received this prize (the medal of Alessandro Volta) at the 230th meeting of ECS in Honolulu 3 October, 2016.

The recipient will have made outstanding achievements in either electrochemical science or solid state science and technology based on publications and/or technical contributions to these fields.

 

Light-Driven Transport of a Liquid Marble with and against Surface Flows

Liquid marbles, that is, liquid drops coated by a hydrophobic powder, do not wet any solid or liquid substrate, making their transport and manipulation both highly desirable and challenging. Herein, we describe the light-driven transport of floating liquid marbles and emphasize a surprising motion behavior. Liquid marbles are deposited on a water solution containing photosensitive surfactants. Irradiation of the solution generates photoreversible Marangoni flows that transport the liquid marbles toward UV light and away from blue light when the thickness of the liquid substrate is large enough (Marangoni regime). Below a critical thickness, the liquid marbles move in the opposite direction to that of the surface flow at a speed increasing with decreasing liquid thickness (anti-Marangoni). We demonstrate that the anti-Marangoni motion is driven by the free surface deformation, which propels the non-wetting marble against the surface flow. We call this behavior “slide effect”.

 

 

N’hésitez pas à consulter le communiqué de presse relatif à cet article : L’effet toboggan ou comment flotter à contre-courant

References:
Light-Driven Transport of a Liquid Marble with and against Surface Flows
Nikita Kavokine, Dr. Manos Anyfantakis, Dr. Mathieu Morel, Dr. Sergii Rudiuk, Dr. Thomas Bickel and Prof. Dr. Damien Baigl
Angew. Chem. Int. Ed. 2016, 55, 11183 –11187
doi: 10.1002/anie.201603639

Lars-Oliver Essen

Lars-Oliver Essen, Professeur à la Philipps-Universität de Marburg est invité par le Laboratoire PASTEUR du Département de Chimie de l’ENS durant le mois de septembre 2016. Son équipe d’accueil est le Groupe de Photochimie Ultrarapide.

Lars-Oliver ESSEN donnera, en qualité de Professeur invité au département de chimie de l’ENS les trois cours suivants :

15/09: Photorécepteurs : Classes, fréquence et fonctions biologiques.

22/09 : Photorécepteurs : Relations structure-fonction dans les photorécepteurs biologiques et bases mécanistiques.

29/09 : Photorécepteurs : Optogénétique, de la structure à l’application.

Ils auront lieu au 29 rue d’Ulm en salle Paul Langevin (1er étage, couloir de gauche) les jeudis 15, 22 et 29 septembre, de 14h à 16h.

 

 

More information on his research :

We use protein crystallography, biophysics and protein chemistry in the following three topics: photobiology, ion-channel engineering and fungal cell wall architecture.

Photobiology: Coming initially from membrane protein crystallography, where we analyzed structures of light-driven ion pumps, we set out to study the molecular mechanism of DNA repair by photolyases. This class of enzymes is indispensable for most sun-exposed organisms to maintain genomic integrity despite damages caused by UV light. Our structures of class I and II photolyases complexed to UV-damaged DNA demonstrate that repair of genotoxic UV-lesions depends on the direct, UV/blue light-driven injection of an electron onto the lesion when bound next to the flavin chromophore. Class II photolyases, present in all plants and most animals, deviate significantly from class I enzymes, raising the question, how the repair of UV-lesions within chromatin-packaged DNA proceeds. We expect that these studies could pave a way to UV-harden domestic plants and livestock.

Phytochromes are not only light switches for plant development, e. g. shade avoidance, but also occur in many photosynthetic and non-photosynthetic eubacteria. Our work on cyanobacterial phytochromes proved that red-light signaling, as exerted by plants, employs a very complex environment for controlling the photoreactivity of their bilin chromophore. Ongoing efforts focus on the nature of structural changes required to mediate down-stream signaling by plant and bacterial phytochromes.

Based on these structural & biochemical data we engineer novel optogenetic tools for exerting light-control on signaling, gene expression or catalysis.

Ion channel engineering: Inspired by the advent of light-controlled channelrhodopsins, ion channels have found wider application in basic sciences like neurobiology. We use wide-pore channels derived from bacterial and mitochondrial porins like OmpF, OmpG and VDAC to reengineer them chemically in terms of specificity and switching characteristics.

Other projects deal with fungal cell wall architecture & adhesion and may hence become relevant for human health and biotechnology. By analyzing the structures and properties of fungal adhesion domains, we showed so far the structural base of flocculation by baker’s yeast, a process important e. g. in beer brewing. Another example, our work on the related Epa protein family from Candida glabrata, an opportunistic human pathogen, may trigger the development of anti-adhesive antimycotics.

 

 

Cellular heterogeneity mediates inherent sensitivity– specificity tradeoff in cancer targeting by synthetic circuits

Synthetic gene circuits are emerging as a versatile means to target cancer with enhanced specificity by combinatorial integration of multiple expression markers. Such circuits must also be tuned to be highly sensitive because escape of even a few cells might be detrimental. However, the error rates of decision-making circuits in light of cellular variability in gene expression have so far remained unexplored. Here, we measure the single-cell response function of a tunable logicANDgate actingon twopromoters in heterogeneous cell populations. Our analysis reveals an inherent tradeoff between specificity and sensitivity that is controlled by the AND gate amplification gain and activation threshold. We implement a tumor-mimicking cellculture model of cancer cells emerging in a background of normal ones, and show that molecular parameters of the synthetic circuits control specificity and sensitivity in a killing assay. This suggests that, beyond the inherent tradeoff, synthetic circuits operating in a heterogeneous environment could be optimized to efficiently target malignant state with minimal loss of specificity.

N’hésitez pas à consulter le communiqué de presse associé à cet article : Des circuits génétiques à l’assaut du cancer

References:
Cellular heterogeneity mediates inherent sensitivity–specificity tradeoff in cancer targeting by synthetic circuits.
Mathieu Morel, Roman Shtrahman, Varda Rotter, Lior Nissim, and Roy H. Bar-Ziv
Proc. Natl. Acad. Sci. USA, 2016
doi: 10.1073/pnas.1604391113

Editorial Advisory Board – ChemPhotoChem

Damien BAIGL, Professeur ENS au Pôle Microfluidique du Département de Chimie, est nommé membre de l’Editorial Advisory Board de ChemPhotoChem, un nouveau journal lancé par ChemPubSoc Europe et edité par Wiley-VCH.

Ce journal international couvrira tous les aspects de la photochimie (principes et applications).

Pour savoir plus sur ChemPhotoChem :

The last decade has seen an explosion in the development of photochemistry, transforming it from a subdiscipline of physical chemistry to a truly multidisciplinary endeavour that has applications in fields ranging from biology and bioanalytical chemistry to materials science and energy research.

As part of the continuing development of the ChemPubSoc Europe family of journals, which includes, among others, Chemistry – A European Journal, ChemPhysChem, ChemElectroChem, ChemSusChem, ChemCatChem, and ChemistryOpen, with Angewandte Chemie as sister journal and the online magazine ChemistryViews, we are happy to announce the newest member: ChemPhotoChem. The journal will be co-owned by sixteen European chemical societies, and will be published by Wiley-VCH, the long-time publishing partner of the German Chemical Society (the relationship goes back to 1921) and the Chemical Publishing Society Europe (ChemPubSoc Europe), an association founded in the late 1990s.

ChemPhotoChem plans to publish Full Papers and Communications alongside invited Reviews, Concepts and Highlights. ChemPhotoChem will cover the entire scope of pure and applied photochemistry, the latter encompassing (inter alia) energy applications, catalysis, photopharmacology and imaging.

 

Dynamical Disorder in the DNA Hydration Shell

The reorientation and hydrogen-bond dynamics of water molecules within the hydration shell of a B-DNA dodecamer, which are of interest for many of its biochemical functions, are investigated via molecular dynamics simulations and an analytic jump model, which provide valuable new molecular level insights into these dynamics. Different sources of heterogeneity in the hydration shell dynamics are determined. First, a pronounced spatial heterogeneity is found at the DNA interface and explained via the jump model by the diversity in local DNA interfacial topographies and DNA− water H-bond interactions. While most of the hydration shell is moderately retarded with respect to the bulk, some water molecules confined in the narrow minor groove exhibit very slow dynamics. An additional source of heterogeneity is found to be caused by the DNA conformational fluctuations, which modulate the water dynamics. The groove widening aids the approach of, and the jump to, a new water H-bond partner. This temporal heterogeneity is especially strong in the minor groove, where groove width fluctuations occur on the same time scale as the water H-bond rearrangements, leading to a strong dynamical disorder. The usual simplifying assumption that hydration shell dynamics is much faster than DNA dynamics is thus not valid; our results show that biomolecular conformational fluctuations are essential to facilitate the water motions and accelerate the hydration dynamics in confined groove sites.

 

 

N’hésitez pas également à consulter le communiqué de presse relatif à cet article : L’eau au coeur de l’ADN

References:
Dynamical Disorder in the DNA Hydration Shell
Elise Duboué-Dijon, Aoife C. Fogarty, James T. Hynes, and Damien Laage
J. Am. Chem. Soc., 2016
doi: 10.1021/jacs.6b02715

Molecular Hydrodynamics from Memory Kernels

The memory kernel for a tagged particle in a fluid, computed from molecular dynamics simulations, decays algebraically as t-3/2. We show how the hydrodynamic Basset-Boussinesq force naturally emerges from this long-time tail and generalize the concept of hydrodynamic added mass. This mass term is negative in the present case of a molecular solute, which is at odds with incompressible hydrodynamics predictions. Lastly, we discuss the various contributions to the friction, the associated time scales, and the crossover between the molecular and hydrodynamic regimes upon increasing the solute radius.

N’hésitez pas à consulter également le communiqué de presse associé à cet article : Un algorithme calculant la mémoire de la dynamique d’un fluide !

References:
Molecular Hydrodynamics from Memory Kernels
Dominika Lesnicki and Rodolphe Vuilleumier ; Antoine Carof and Benjamin Rotenberg
Physical Review Letters 116, 147804 (2016)
DOI: 10.1103/PhysRevLett.116.147804

Subventions scientifiques de la Fondation Simone et Cino Del Duca

Damien BAIGL, Pôle Microfluidique du Département de Chimie, a obtenu l’une des trois subventions scientifiques 2016 de la Fondation Simone et Cino Del Duca délivrées par l’Institut de France.

La Fondation Simone et Cino Del Duca de l’Institut de France décerne chaque année, alternativement au titre des disciplines relevant des deux divisions de l’’Académie des sciences sur proposition d’’un jury constitué de membres de l’’Académie des sciences, trois subventions distinctes destinées à de jeunes équipes françaises, le chef d’’équipe devant être âgé de moins de 45 ans (dans l’’année d’’attribution du prix), conduisant des projets de recherche dans les disciplines suivantes :

– Chimie;

– Biologie, moléculaire et cellulaire, génomique;

– Biologie intégrative;

– Biologie humaine et sciences médicales et leurs applications.

David E. Manolopoulos

David E. Manolopoulos, Professeur de Chimie Théorique à Oxford est invité par le Département de Chimie de l’ENS durant les mois d’avril et mai 2016.

Il est l’un des pionniers de l’étude des effets quantiques nucléaires et plus récemment il s’est intéressé à la chimie des spins impliqués par exemple dans l’orientation magnétique lors du déplacement des oiseaux

 

 

More important contributions :

David Manolopoulos has made contributions to a wide variety of areas in theoretical chemistry. His spiral algorithm for generating carbon clusters underlies the IUPAC classification of fullerene isomers and has led to numerous experimentally-confirmed predictions of the structures and properties of higher fullerenes. The Atlas of Fullerenes that he wrote with Patrick Fowler in 1995 is now the standard reference for work in this field. His quantum mechanical calculations in chemical reaction dynamics have explained a number of important experimental results and led to an improved understanding of reactive transition states, the role of resonances in hydrogen atom transfer reactions, the statistical nature of insertion reactions that proceed via deep potential energy wells, the importance of electronically non-adiabatic effects in chemical reaction dynamics, and the effect of long-range forces on chemical reactions. The numerical methods and computer programs that he developed to perform these calculations are still widely used by the gas phase chemical reaction dynamics community and by those interested in cold and ultra-cold atomic and molecular collisions. His more recent work on condensed phase dynamics shows great promise for elucidating quantum mechanical effects in liquids and in light-atom transfer reactions in chemical and biochemical systems. His ring polymer molecular dynamics (RPMD) method is rapidly emerging as an effective tool for simulating a wide variety of processes ranging from polyatomic chemical reactions in the gas phase through the dynamics of liquid water and aqueous solutions to enzyme-catalysed hydride, proton, and proton-coupled electron transfer reactions.