Rozprawy doktorskie na temat „Modelage Biophysique”
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Fernandes, Gonçalo. "Imaging transcription in living embryos to decipher the robustness of patterning". Electronic Thesis or Diss., Université Paris sciences et lettres, 2022. http://www.theses.fr/2022UPSLS025.
Pełny tekst źródłaMorphogen gradients provide concentration-dependent positional information required to establish the polarity of developmental axes. Although the critical role of these gradients is well recognized, it is unclear how they provide reproducible expression patterns. This is particularly surprising if we consider the stochastic nature of transcription.To address this question, I focus on the establishment of the anterior-posterior (AP) axis of fruit fly embryos, which is mostly defined by Bicoid (Bcd), a very well-characterized morphogen and transcription factor. bcd mRNAs are expressed maternally and anchored at the anterior tip of the oocyte. After egg laying, these mRNAs are translated into proteins, which diffuse through the cytoplasm and form a gradient with its highest concentration at the anterior. A simple model is that depending on their position along the AP axis and thus on Bcd concentration, cells will adopt different fates. However, long debates in the field have questioned the possibility that Bcd-dependent transcription patterns emerge solely from diffusive biochemical interactions between limiting amounts of Bcd molecules and the gene promoter region.The goal of my PhD was to determine how Bcd precisely regulates expression of its main target gene, hunchback (hb). For this, I adapted to synthetic reporters the MS2-MCP system, which allows the fluorescent tagging of mRNAs and provides, thus, a quantitative analysis of transcription dynamics at high spatiotemporal resolution in living embryos. In these reporters, the MS2 sequence was placed under the control of a minimal promoter also containing DNA binding sites for Bcd and/or its known partners, Hb and Zelda (Zld), either alone or in combination. My goal was to determine how the various reporters could recapitulate expression of the hb promoter (hb-MS2 reporter) and shed light on the specific roles of the different factors and their interactions in the transcription mechanism.Interestingly, expression of the reporter with only nine Bcd binding sites (three more than in the hb gene) matches almost perfectly the hb-MS2 reporter pattern, except for the very high steepness of the expression domain boundary and the speed to reach steady-state. This suggests that Bcd alone is the main source of positional information, defining the positioning of the boundary but not its steepness nor the speed of its establishment.In addition, binding of Bcd’s partners to the promoter speed-up the process by acting in different steps of the transcription mechanism: i) Hb synergizes with Bcd by reducing transcription burstiness and increasing the polymerase firing rate; ii) Zld lowers the Bcd concentration threshold required for Bcd-dependent expression. In collaboration with physicists, a biophysical model of Bcd-dependent expression was developed providing a theoretical framework for the experimental data. This model showed that the very rapid establishment of the hb expression boundary can be solely explained by an equilibrium model involving the binding of Bcd molecules to their DNA-binding sites for positional information which requires Zld and Hb for its temporal dynamics.To further confirm that Bcd is the sole source of positional information for hb expression, I compared the boundary position of the Bcd-only dependent reporters in embryos expressing one dose or half dose of Bcd. Surprisingly, the corresponding shifts of these reporters’ boundaries upon one vs half dose of Bcd were smaller than theoretically expected given the measured decay length of the Bcd protein gradient. This indicates a shorter decay length for the Bcd activity gradient and suggests the existence of different Bcd populations, with some Bcd molecules being less active than others. Importantly, the shift observed for the hb-MS2 reporter was the same as for the Bcd-only dependent reporters confirming Bcd as the sole source of positional information for hb expression
VRIGNEAUD, JEAN-MARC. "Developpement d'un modele biophysique pour l'evaluation des dommages radio-induits dans la fibre chromosomique". Toulouse 3, 2000. http://www.theses.fr/2000TOU30054.
Pełny tekst źródłaRanchon, Isabelle. "La photodegenerescence retinienne : quantification d'un modele et place des radicaux libres dans le processus degeneratif (doctorat : biophysique sensorielle)". Clermont-Ferrand 1, 1999. http://www.theses.fr/1999CLF1PP01.
Pełny tekst źródłaVermeulen, Arthur. "Modélisation biophysique du neurone récepteur olfactif : influence de la structure spatiale du neurone, de l'environnement sensillaire et de la rétropropagation des potentiels d'action sur le codage de l'intensité olfactive". Grenoble INPG, 1997. http://www.theses.fr/1997INPG0156.
Pełny tekst źródłaColloc'h, Nathalie. "Analyse qualitative des surfaces moleculaires a l'aide de fonctions de lissage b-spline et etudes topologiques quantitatives : application aux proteines". Paris 6, 1988. http://www.theses.fr/1988PA066162.
Pełny tekst źródłaMouttahar, Abdelhak. "Etude du comportement mecanique d'une coque anisotrope et fibreuse : application a la mecanique ventriculaire gauche". Toulouse 3, 1987. http://www.theses.fr/1987TOU30168.
Pełny tekst źródłaDavid, Laurent. "Modelisation des interactions electrostatiques des biomolecules en solution". Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10159.
Pełny tekst źródłaKhalid, Naciri Jaâfar. "Modelisation d'ecoulements instationnaires en conduites deformables : applications aux ecoulements arteriels". Toulouse 3, 1988. http://www.theses.fr/1988TOU30052.
Pełny tekst źródłaPavard-Ohanessian, Jacqueline. "Contribution à l'étude de la stéréochimie des chaines glycaniques de glycoprotéines et à l'étude de leurs interactions avec la lectine d'arachide spécifique des substrats d-galactosyles terminaux". Paris 13, 1986. http://www.theses.fr/1986PA132005.
Pełny tekst źródłaCordier, Florence. "Développements méthodologiques et études dynamiques de protéines en solution par relaxation en RMN". Université Joseph Fourier (Grenoble ; 1971-2015), 1998. http://www.theses.fr/1998GRE10090.
Pełny tekst źródłaFurois-Corbin, Sylvie. "Contribution à l'étude théorique des biopolymères : acides nucléiques et protéines membranaires". Paris 6, 1987. http://www.theses.fr/1987PA066384.
Pełny tekst źródłaSaadat, Abdelkader. "Etude de la mobilite moleculaire du collagene par courants thermostimules : modelisation du vieillissement cutane". Toulouse 3, 1988. http://www.theses.fr/1988TOU30178.
Pełny tekst źródłaAmerein, Béatrice. "Modelisation et representation dynamique de macromolecules biologiques". Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR13040.
Pełny tekst źródłaEtchebest, Catherine. "Etudes theoriques d'un canal ionique transmembranaire : la gramicidine a". Paris 6, 1987. http://www.theses.fr/1987PA066049.
Pełny tekst źródłaSaad, Mohamed. "Études structurales à basse résolution par diffraction de rayons X synchrotron des fibres de collagène dans le tendon : Détermination des facteurs de structure, évaluation des méthodes du remplacement isomorphe et autres modélisations". Grenoble 1, 1994. http://www.theses.fr/1994GRE10187.
Pełny tekst źródłaCoppel, Yannick. "Études de la structure de complexes ADN-ligand par résonance magnétique nucléaire et modélisation nucléaire : sondes de chiralite de l'ADN, modèles d'AP-endonuclease". Université Joseph Fourier (Grenoble ; 1971-2015), 1996. http://www.theses.fr/1996GRE10079.
Pełny tekst źródłaCELIA, HERVE. "Etudes structurales de la sous-unite b de la gyrase d'escherichia coli et de l'arn polymerase a de saccharomyces cerevisiae. Microscopie electronique et analyse d'images de cristaux bidimensionnels". Strasbourg 1, 1993. http://www.theses.fr/1993STR13175.
Pełny tekst źródłaGruza, Jan. "Modélisation de la flexibilité des glycannes complexes en solution et en interaction avec des protéines". Grenoble 1, 1998. http://www.theses.fr/1998GRE10158.
Pełny tekst źródłaMorelle, Nathalie. "Attribution assistée par ordinateur des spectres RMN de protéines : application à l'étude structurale des ferrocytochromes c555 de Chlorobium limicola f. thiosulfatophilum et c2 de Rhodobacter capsulatus". Université Joseph Fourier (Grenoble), 1995. http://www.theses.fr/1995GRE10166.
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