PhD defenses

Congratulations to our new doctor Mael Montevil who graduated with the very Honourable grade and congratulations of the Jury on October 7th 2011



Thesis title : Biological time and extended critical transitions : towards and objectivization of the living state of matter.

Abstract :

Congratulations to our new doctor Getao SHI who graduated with the very remarkable grade on October 17th 2011



Thesis title : Development of functional proteomics approcahes for studying retrograde transport
The thesis defense took place at 9:30am on October 17th 2011 in Amphithéâtre Constant Burg(downstairs of the building) of Curie Institute.

Abstract :

Congratulations to our new doctor Kevin Ho Wan with the very Honourable grade and congratulations of the Jury on September 30th 2011



Thesis title : Single-Molecule Studies of the Bacterial Transcription Coupled Repair Process

Abstract :

Transcription coupled repair (TCR), a sub-pathway of the nucleotide excision repair mechanism, is activated when a RNA polymerase (RNAP) is arrested during transcription by DNA damage. TCR is a ubiquitous cellular response important for maintenance of DNA integrity. Some human genetic disorders are associated with defect on TCR, like the Cockayne syndrome for instance. In the bacterium Escherichia coli, TRCF, the product of the mfd gene, is the DNA translocase that couples transcription and DNA repair: it recognizes a stalled ternary elongation complex, dissociates it, and recruits the UvrABC repair machinery.
We used a single molecule approach, by means of magnetic tweezers, to study the initiation of TCR and monitored the dissociation of individual RNAPs by individual TRCFs in real time. We have identified that TRCF acts on stalled RNAP by remodeling the transcription bubble in two successive ATP-dependent steps separated by a novel intermediate denoted RD*.
Statistical analysis of the time required to dissociate the stalled RNAP at different concentrations of TRCF has shown that the displacement of the ternary elongation complex is a three limiting-steps process: (i) recruitment of TRCF to the stalled RNAP, (ii) activation of TRCF and initiation of the dissociation of RNAP by rewinding of 2/3 of the "transcription bubble", and (iii) complete dissociation of the elongation complex. The intermediate complex RD* formed after the first step of rewinding is characterized by a long lifetime, which suggests that it would behave as a temporally reliable marker, enabling the recruitment of the UvrABC repair machinery to the damaged site.

Congratulations to our new doctor Kathleen Zylbersztejn who graduated with the very Honourablme grade and congratulations of the Jury on September 15th 2011


Kathleen Zylbersztejn (left) with PhD colleagues Lydia, Maja, Imène and Francesca (FdV).

Thesis title : role of vesicular traffic in axon guidance

Abstract :

Congratulations to our new doctor Ruben Elisée who graduated with congratulations of the Jury !

His thesis defense took place on September 9th 2011 in the Pasteur Institute in Paris.

Thesis title
Analysis of mitochondrial metabolism in response to peptidoglycan in epithelial cell"
(in french) : "La réponse métabolique de cellules épithéliales au peptidoglycane"

Noah Hardy, FdV teacher, had the chance to attend Ruben Elisée's thesis defense and wrote us a report of this Event :

Congratulations to our new doctor Thomas Julou who graduated on June 9th 2011 !

Her thesis defense took place at the Ecole Normale Supérieure Physics Departement in Paris.

Thesis title
« Evolution, competition and cooperation in bacterial populations »

Members of the Jury
Didier Chatenay (CNRS 3231, Paris), President
Ivan Matic (Inserm U1001, Paris)
Sam Brown (University of Edinburgh, UK)
Pierre Cornelis (Vrije Universiteit Brussels)
David Bensimon (CNRS, ENS Paris), Supervisor
Nicolas Desprat (Université Paris Diderot)

Abstract
The interplay of environment, heritability, and stochasticity results in the development of different individuals starting from a given genotype. This phenotypic variability affects how natural selection acts on genetic variability. From a general perspective, I aim at studying the impact of phenotypic variability on adaptive dynamics.
In the first chapter, I report on the design of an evolutionary experiment in a structured environment using Escherichia coli. The trait under selection is resistance to high temperature. In particular, we study the effects of high temperature on chemotaxis, as well as the impact of acclimation on growth and survival at high temperature.
The second chapter is about the development of a microbial population measurement device dedicated to diluted populations. This continuous, non-invasive measurement has a low detection limit that depends on the species. For the model species Escherichia ecoli, the limit is ca. 5000/mL which represents a 100-fold improvement compared to classical photometric methods.
In the third chapter, we study the distribution of pyoverdine between individuals of a clonal population of Pseudomonas aeruginosa. The variability of the concentration of this siderophore is much greater than expected. Although pyoverdine is considered to be a public good, neither spatial heterogeneity nor heritability provide a meaningful description of the variability. Instead we characterize rapid fluctuations in pyoverdine concentration, and propose a model based on a phenotypic switch in pyoverdine metabolism that is in good agreement with the experimental data.

Congratulations to our new doctor Hélène Duponti's who graduated with congratulations of the Jury !

Her thesis defense took place on April 29th 2011 in the Institut de Paléontologie Humaine.

Thesis title (in french)
« Modélisation multi-agents d'un service écosystémique, scénarios de systèmes d'équarrissage par des rapaces nécrophages »

Members of the Jury
Abbadie Luc, Professeur à l'université Paris VI et directeur du laboratoire BIOEMCO, Examinateur
Bergandi Donato, Maître de conférences au MNHN, Rapporteur
Bobbé Sophie, Chercheure associée au Centre Edgar Morin CNRS/EHESS, Co-Directrice de thèse
Fritz Hervé, Directeur de recherche CNRS, Rapporteur
Larrère Raphaël, Directeur de recherche INRA, Examinateur
Le Page Christophe, Cadre de recherche CIRAD, Examinateur
Mathevet Raphaël, Chargé de recherche CNRS, Examinateur
Sarrazin François, Professeur Université Paris VI, Directeur de thèse

Abstract (in french)

La conservation des vautours dépend en partie de la gestion de leurs ressources trophiques, qui, en Europe, est largement liée aux activités pastorales et contrainte par les réglementations sanitaires. Cependant, par leur régime alimentaire charognard, les vautours rendent des services écosystémiques. Ainsi, la mise à disposition de carcasses à ces rapaces nécrophages peut être envisagée comme favorable, puisqu'elle permet de préserver des espèces emblématiques et de maintenir les services qu'elles offrent.

En s'appuyant sur des entretiens ethnologiques et des données écologiques, cette étude sur l'équarrissage naturel dans le contexte agropastoral qui est le sien, a été menée selon une approche interdisciplinaire. Suivant les préconisations issues du Millenium Ecosystem Assessment (M.E.A.), un modèle a été développé en vue d'explorer les « réactions » de ce service à des pratiques humaines. Dans notre cas, il s'agissait d'évaluer les conséquences de modes de gestion locale de l'équarrissage sur une population de vautours et sur des bénéfices environnementaux et économiques qu'elle génère. Au moyen de la modélisation multi-agents, un modèle à caractère générique a été développé. Il représente explicitement les comportements d'alimentation d'une population de vautours fauves - constituant « l'offre » de service -, et la mise à disposition des carcasses aux vautours- représentant la « demande » pour le service. L'offre fluctue selon la dynamique de population de vautours. La demande varie selon les pratiques agropastorales qui influencent la mortalité des troupeaux, et les choix de pratiques d'équarrissage des éleveurs.

Les résultats montrent que les conséquences environnementales et économiques de l'équarrissage dépendent avant tout des dispositifs d'équarrissage mis en place sur un même site, sachant que l'équarrissage naturel peut prendre plusieurs formes. A ce propos, les résultats soulignent les avantages de l'utilisation d'un dispositif d'équarrissage naturel géré directement par chaque éleveur, la placette. Néanmoins, les bénéfices offerts par une population de vautours, comme la pérennité de celle-ci, dépende de l'utilisation ce dispositif. Or, les manières d'envisager le recours à l'équarrissage naturel relèvent avant tout de représentations sociales variées des éleveurs et de leurs relations aux autres acteurs de l'équarrissage. Le recours à l'équarrissage naturel ne correspond pas toujours aux capacités d'élimination des carcasses des vautours. Lorsque la demande et l'offre sont en décalage, des conséquences négatives pour les humains comme les vautours peuvent survenir. L'ajustement de la mise à disposition des carcasses aux besoins alimentaires des vautours est de première importance pour assurer une gestion à long terme de l'équarrissage en y intégrant les vautours. Enfin, l'adaptation du modèle à une situation existante révèle l'importance de resituer l'étude dans un contexte particulier en vue de recommander des mesures de gestion.

Les approches interdisciplinaires offrent la possibilité d'une certaine réflexivité sur le processus de recherche. A partir des rapports à la modélisation des chercheurs en sciences sociales et des écologues, l'intégration des dimensions sociales dans la modélisation de systèmes socio-écologiques est discutée. Nous soulignons les avantages de la participation de chercheurs en sciences sociales dans les approches de modélisation pour la conservation. Enfin, les implications théoriques, actuelles et potentielles d'envisager les rapaces nécrophages comme des producteurs de service en vue de leur conservation, sont explorées. Elles sont replacées dans une perspective plus large, pour reconsidérer la pertinence du concept de service écosystémique -tel que mobilisé par le M.E.A.- pour la conservation de la nature.

Keywords (in french) : équarrissage ; Vautour fauve ; service écosystémique ; interdisciplinarité ; système socio-écologique ; modélisation multi-agents ; conservation des espèces.

Congratulations to our new doctor Marianne Mugabo that graduated with the very honourable grade !

Her thesis defense took place on April 11th 2011 in the Ecole Normale Supérieure in Paris.

Thesis title (in french)
Structure de population et histoire de vie chez le lézard vivipare"

Thesis co-supervisors : Jean-François Le Galliard and Régis Ferrière.

Members of the Jury
Jean-Michel Gaillard (rapporteur)
Christophe Barbraud (rapporteur)
Tim Benton (examinateur)
Anne Charmantier (examinatrice)
François Sarrazin (examinateur)
Michel Morange (examinateur)

Abstract (in french)

La structure des populations influence de manière importante le taux de croissance des populations et donc leurs capacités à faire face à des changements environnementaux. En effet, elle détermine la part d'individus qui contribuent au renouvellement des générations ainsi que l'intensité des interactions sociales compétitives et coopératives. Utilisant le lézard vivipare (Zootoca vivipara, Jacquin 1787) comme modèle d'étude, mon travail de thèse consiste à caractériser la relation entre la structure de population (en termes de cohortes, densité et classes d'âge et de sexe), l'histoire de vie et la dynamique de petites populations isolées. Pour cela, nous combinons des approches expérimentales en conditions semi-naturelles à des approches théoriques utilisant des modèles populationnels à un et deux sexes structurés en classes d'âge. Une analyse critique de la littérature montre que la variabilité environnementale peut générer des différences d'histoire de vie entre cohortes de naissance, ou effets cohortes, à travers son influence sur la qualité des individus et sur l'intensité de la compétition intraspécifique au sein d'une cohorte et entre cohortes. Un premier travail empirique démontre que ces troismécanismes induisent de la variation d'histoire de vie entre cohortes, mais met également en évidence que les effets directs de la variabilité environnementale sur la qualité des individus interagissent de manière complexe avec des effets indirects sur l'intensité de la compétition entre individus. Au cours d'une deuxième étude empirique, nous analysons les processus et conséquences démographiques de ces interactions compétitives.
Une élévation de la densité augmente la compétition trophique et pourrait également induire des réponses hormonales au stress social, ce qui ralentit la croissance corporelle et la reproduction. Un modèle stochastique démontre que cette densité dépendance de l'histoire de vie interagit avec les fluctuations stochastiques du sexe ratio pour façonner la dynamique d'extinction des petites populations de lézards. Ces prédictions seront affinées par l'analyse d'une troisième étude empirique impliquant une manipulation conjointe de la densité et du sexe ratio de la population. Nos résultats, intégrés dans le contexte général de l'écologie des populations, soulignent l'importance de prendre en compte la structure de la population et l'hétérogénéité de l'histoire de vie pour établir des prédictions fiables sur le devenir des petites populations et mettre en place des mesures de gestion efficaces.

Keywords (in french) : effets cohortes, densité dépendance, structure d'âge, sexe ratio adulte, histoire de vie, système d'appariement, sélection sexuelle.

Congratulations to our new doctor Minale Ouethrani's who graduated with the very honourable grade !

Her thesis defense took place on March 25th 2011 in Agroparistech Centre de Paris Claude Bernard,

Thesis :
Chemical contaminants in coffee: developpement of analytical methods and investigation of their bioavailability

Abstract :
Coffee brew is one of the most frequent drinks consumed in the world, but its health effects
are still in debate as it remains a heterogeneous complex matrix. Even though some of its
major constituents have a beneficial health effect (i.e polyphenols), toxic organic
contaminants are also present such as OTA, PAHs or acrylamide. The role of the gut
microbiota in the metabolism of such contaminants has been often overlooked and is a crucial
step in risk assessment. After the development of a straightforward analytical method for the
simultaneous quantification of the targeted compounds using a semi-automated solid-phase
extraction procedure with HPLC-FLD analysis, we used in vitro methodologies to study the
metabolism of coffee contaminants by the human gut microbiota. Batch cultures as well as
SHIME experiments showed that the human gut microbiota is able to degrade OTA with
formation of OTα and OTB (newly microbial metabolite identified in vitro) which can be
considered as a detoxification pathway. Using the SHIME, we have also investigated the
effects of OTA and its association with coffee brew on the human gut microbiota by
monitoring the fermentation activity and the composition of the microbiota by TTGE and
DGGE. Major fermentation shifts were observed during the coffee + OTA period throughout
a more important production of SCFAs and a paralleled decrease in ammonium. While no
major change was observed within the dominant bacterial populations, notable changes could
be observed towards Lactobacillus and Bifidobacterium species. In particular, L. reuteri was
found to be greatly reduced by OTA. Further research is needed to study the possible
consequences on the host physiology.

Congratulations to our new doctor : Jeremie BARRAL who graduated last February 8th 2011 with the congratulations of the Jury !

Hair-bundle amplification by sensory hair cells from the inner ear
The vertebrate ear benefits from nonlinear mechanical amplification to operate over a vast range of sound intensities. The amplificatory process is thought to emerge from active force production by sensory hair cells. The mechano-sensory hair bundle that protrudes from the apical surface of each hair cell can oscillate spontaneously and function as a frequency-selective, nonlinear amplifier.
By analyzing the dynamics of a bullfrog's sacculus hair bundle immersed in various viscous milieus, we evaluated the effect of hydrodynamic friction. We observed that intrinsic fluctuations, owing to the small number of molecules inside the hair bundle, are the dominant source of noise that jostle the hair-bundle response weak stimuli and seriously limit amplification.
Most hair bundles are mechanically coupled by overlying gelatinous structures. By combining dynamic force clamp of a hair bundle with real-time stochastic simulations of hair-bundle mechanics, we could mimic a virtual environment in which a real hair-bundle is elastically coupled to two neighbors. We found that coupling increased the coherence of spontaneous hair-bundle oscillations
by effectively reducing noise. We argue that the auditory amplifier relies on hair-bundle cooperation to overcome intrinsic noise limitations and achieve high sensitivity and sharp frequency selectivity.
Nonlinear amplification is the price to pay for high sensitivity. Two-tone timulation of a single hair bundle generates distortion products and manifests masking phenomena. We showed that the effects of nonlinear mechano-transduction are amplified near the characteristic frequency of spontaneous hair-bundle oscillations. We thus argue that human psychophysical observations, cochlear mechanics and active hair-bundle oscillations rely on the generic behaviour of active nonlinear oscillators that shapes the sensation of sounds at the periphery of the auditory system.

L'amplificateur ciliaire des cellules ciliées de l'oreille interne
L'audition des vertébrés bénéficie d'un dispositif d'amplification non-linéaire afin de détecter une large gamme d'intensités sonores. Le mécanisme sous-jacent pourrait provenir de la production active de force par les cellules ciliées sensorielles. La touffe ciliaire mécano-sensorielle qui projette
de la surface apicale de chaque cellule ciliée peut osciller spontanément et agir comme un amplificateur non-linéaire sélectif autour d'une fréquence caractéristique.
En analysant la dynamique d'une touffe ciliaire issue du saccule de la grenouille taureau immergées dans différents milieux visqueux, nous avons évalué l'effet de la friction hydrodynamique.
Nous avons observé que les fluctuations intrinsèques, dues au faible nombre de molécules
composants la touffe ciliaire, sont la source dominante de bruit qui brouille la réponse de la touffe
ciliaire aux petits stimuli et limite dramatiquement l'amplification.
La plupart des touffes ciliaires sont mécaniquement couplées par des membranes
gélatineuses. En combinant application de force et simulation stochastique en temps réel de la
mécanique de la touffe ciliaire, nous avons mimé un environnement virtuel dans lequel une touffe ciliaire réelle est élastiquement couplée à deux voisines. Nous avons mis en lumière l'effet du couplage sur l'augmentation de la cohérence de phase et la réduction du bruit. Ces résultats indiquent que l'amplificateur auditif dépend de la coopération entre touffes ciliaires voisines afin d'accroître la sensibilité et la sélectivité fréquentielle de la détection auditive.
L'amplification non-linéaire est le prix à payer pour la sensibilité. La réponse d'une touffe ciliaire à un stimulus complexe présente l'émergence de produits de distorsion et de phénomènes de masquages. Nous avons montré que les effets non-linéaires de la mécano-transduction sont amplifiés près de la fréquence caractéristique de l'oscillation spontanée. Nous soutenons que les
observations psychoacoustiques, la mécanique cochléaire ainsi que les oscillations ciliaires spontanées dépendent du comportement générique d'oscillateurs actifs non-linéaires qui façonnent la sensation sonore à la périphérie du système auditif.

Jeremie Barral was a PhD student at Laboratoire Physico-Chimie Curie
CNRS, Institut Curie, UPMC, Université Paris-Diderot

Congratulations to our new doctor : Alice DEMAREZ who graduated with the congratulations of the Jury !

Ph D Title : "Investigating proteostasis and ageing of Escherichia coli using spatio-temporal algorithms"

Abstract :
An increase in the probability of death and a decrease in the reproduction rate (both accounting for decrease of the fitness) are signatures of ageing in living organisms. Using a morphological criteria, allowed to demonstrate that Escherichia coli a symmetrically dividing micro-organism is subject to ageing.

Ageing is studied by using time-lapse movie of growth of microcolonies emanating from a single cells. This result in a huge amount of images to analyse. The duration of semi- or non-automated analyses of those images brings a serious limit to the rate of data available for statistical and biological analysis. Hence, the processing of images had to be automated to speed up the process and make possible the studies of large data set. To address this key issue, I developed a new approach based on one main idea: considering segmentation and tracking at the same time, whereby the spatio-temporal segmentation uses the advantage of the large time redundancy of data, contrary to existing methods relying on successive spatial segmentation and tracking.

Specifically, I applied the image analysis tools to address the role of protein aggregation in bacterial ageing. Aggregation of misfolded proteins is known to be an hallmark of many age-related disease e.g. Alzheimer disease, Parkinson disease, cataract, and known to have cell toxicity action. Thanks to a translational fusion between a small heat shock protein (IbpA) and a fluorescent protein, effect of natural protein aggregation on growth rate of bacteria were observed. We were able to show, among other things, that protein aggregation is associated with the decrease of growth rate associated with ageing in E. coli .

In conclusion in this work I developed new image analysis methodologies that improved speed, accuracy and reliability of the results on one hand, and shed light on the dynamics and effects of natural aggregates in bacterial ageing on the other hand.

Congratulations to our new Doctor : Arnaud Pocheville
who graduated on Wednesday December 15th 2010 (thesis defense at ENS).

"La Niche Ecologique, Concepts, Modèles, Applications"
(PhD defense in French))

Résumé:
Cette thèse est une enquête sur le concept de niche et quelques grands cadres théoriques qui y sont apparentés: la théorie de la niche et la théorie neutraliste en écologie, la théorie de la construction de niche en biologie évolutive, et la niche des cellules souches en écologie intra-organisme.
Dans une première partie nous retraçons l'histoire du concept de niche et confronte la théorie de la niche à une théorie concurrente, la théorie neutraliste. Le concept de niche apparaît comme devant être un explanans de la diversité des espèces et de la structure des écosystèmes.
Nous confrontons ensuite la théorie évolutive standard à la théorie de la construction de niche, dans laquelle un organisme peut modifier son environnement et ainsi influer sur la sélection à venir. Nous montrons comment caractériser cette confrontation en termes d'échelles temporelles des processus en jeu, ce qui nous permet d'identifier le domaine de validité véritablement propre à la théorie de la construction de niche plus explicitement qu'il ne l'a été par le passé.
Enfin, nous développons les recherches des deux parties précédentes dans le cadre de la modélisation d'une thérapie génique comme un processus écologique de compétition et de construction de niche par les cellules. Nous présentons une famille de modèles appliqués à différentes échelles temporelles de la dynamique cellulaire, entre lesquelles le modélisateur précautionneux ne saurait choisir sans résultats expérimentaux spécifiques.
Nous concluons sur les conceptions de la relation entre un organisme et son environnement attachées aux diverses facettes du concept.

English Summary:
This thesis is an investigation of the niche concept and of some related major theoretical frameworks: the niche theory and neutral theory in ecology, the niche construction theory in evolutionary biology, and stem cell niche in intra-organism ecology.
In the first part we trace the history of the niche concept and compares the niche theory to a competing theory, the neutral theory. The niche concept appears to be an explanans of species diversity and ecosystem structure.
Then, we compare the standard evolutionary theory to the theory of niche construction, in which an organism can affect its environment and thus influence the selection to come. We show how to characterize this confrontation in terms of time scales of processes involved, which allows us to identify the range of validity truly unique to the theory of niche construction more explicitly than it has been in the past.
Finally, we develop the research of the previous two parts in the modeling of a gene therapy as a process of competition and ecological niche construction by cells. We present a family of models applied to different time scales of cellular dynamics, among which the modeler can not choose without specific experimental results.
We conclude on the conceptions of the relationship between an organism and its environment attached to the various facets of the concept.

CONGRATULATIONS TO OUR NEW DOCTOR, Natalya Jukovskaya who graduated with the Very Honorable grade !


Natalya Jukovskaya presented her PhD defense on December 14th at the CRI,Paris Descartes University, Faculty of medicine.

PhD title : "Peripheral adaptation to odors in the rodent olfactory bulb: recordings and consequences on the local functional hyperemia"

Abstract: Functional Magnetic Resonance Imaging technique (fMRI) uses hemodynamic changes in the brain for mapping neuronal activity. Although it is recognized that functional hyperemia is triggered by neurotransmitter release rather than energy consumption by activated neurons, the mechanisms which link neuronal activity and hemodynamic changes are still under debate. We used the olfactory bulb as a biological model to study the relationship between the amount of locally released glutamate from olfactory receptor neuron terminals and blood flow changes in capillaries. We used two-photon laser scanning microscopy to measure in parallel with high spatial and temporal resolution vascular responses in individual capillaries and Ca2+ variations in the terminals of Olfactory Sensory Neurons (OSN).
Here we report that functional hyperemia is positively or negatively coupled to the amount of the locally released glutamate as measured for Ca2+ signals, depending on the absence or the presence of peripheral adaptation. In parallel we investigated the extent for which OSNs are activated homogeneously. We report that during peripheral adaptation OSN terminals are not homogeneously activated.

Keywords: Olfactory bulb, neurovascular coupling, calcium imaging, two-photon microscopy, in vivo, blood flow.

CONGRATULATIONS TO OUR NEW DOCTOR, Sandrine ADIBA who graduated with the Very honorable grade !



Sandrine ADIBA presented her PhD defense on December 13th 2010 in the Auditorium de Jussieu UPMC.

PhD title : "Natural selection and genetic drift effects on neutral polymorphism"

Members of the Jury :
Pierre Cosson, Genève, rapporteur
Christine Paillard, Brest, rapporteur
Delphine Sicard, Le moulon, examinateur
Amaury Lambert, UPMC, examinateur
Minus van Baalen, UPMC/ENS, directeur de thèse
Frantz Depaulis, ENS, co-directeur de thèse

Abstract :
Diversity is essential for all living organisms, it provides the basis for the species evolvability and their ability to adapt to environmental variations. Determining the factors contributing at the origin, the maintenance of the genetic variance observed remain central and fundamental research issues. The aim of this study was to understand evolutionary factors maintaining neutral polymorphism. The influence of the natural selection and genetic drift processes being complex, we developed complementary experimental and theoretical approaches to disentangle selective and drift contribution.
Using the biological model Escherichia coli and Dictyostelium discoideum, we first studied the natural variability of interactions between the two species. In the second part, we tested for bacterial traits involved in this natural variability. We found that bacteria carrying virulence genes were resistant to the amoeba grazing. This result was in agreement with the coincidental evolution hypothesis of virulence factors.
We then focus on population genetics aspects of our biological system. In our coevolution experiments, we followed bacterial allele frequency variations during 300 bacterial generations and in four environmental conditions: with or without biotic factor and with or without spatial structure. Our results did not depart from genetic drift predictions. The theoretical model developed addressed demographic stochasticity effects on neutral allele fixation probability and time to fixation. We found that the fixation probability and the time to fixation were affected by the demographic stochasticity compared to a model with a population of constant size (Moran model).

Key words: natural selection, genetic drift, polymorphism, coevolution, virulence, bacteria, amoeba, fixation.

Ecole doctorale : Frontières du Vivant ED474 Liliane Bettencourt

CONGRATULATIONS TO OUR NEW DOCTOR, Christophe BECAVIN, who graduated with the Very honorable grade !


Christophe BECAVIN presented his PhD defense on December 2h 2010 at the Paris Descartes University, Faculty of medicine Amphithéâtre Lutton.

Thesis title : ""Dimensionality reduction and pathway network analysis of transcriptomic data: Application to T-cell characterization""

Members of the jury :
Rapporteurs: Alain Arneodo, Laboratoire Joliot-Curie, ENS Lyon
Lars Rogge, Institut Pasteur, Paris
Examinateurs: Jean-Marc Victor, LPTMC, Paris 6
Sylviane Pied, Institut Pasteur, Lille
Andrei Zinovyev, Institut Curie, Paris
Thesis supervisor : Arndt Benecke, IHES, Paris


Abstract :
In the context of whole-genome expression (transcriptome) data analysis, different tools already exist today. One class of tools, called
dimensionality reduction techniques, seeks for general patterns and important components of the system which can help to summarize the data.
During my thesis I extensively studied the different state-of-the-art techniques existing in this field. We then developed our own approach based on the combination of Singular Value Decomposition and Multidimensional Scaling. We proved its usefulness and accuracy.
In addition to gene expression-specific data analysis tools, we developed a software which allows to map different gene expression patterns to protein-protein networks. In order to link the gene expression scale to the protein scale (proteome). Those protein-protein networks are built based on curated ontology-based pathway models.

The tools developed here and many others were used in order to analyze different "omics" data. The first application was on the analysis of experiments measuring autoantibodies and cytokine expression in the human
body during Malaria infection. We determined specific markers of Cerebral Malaria, which will help to better detect the disease. The larger analysis we have performed, consisted in defining the transcriptome profile of regulatory T-cell subsets (Treg). These cells are depleted during HIV infection, for this reason a good molecular characterization of the different subsets would help find more accurate markers to, for example, follow their evolution during the treatment with novel drugs to fight AIDS. Among the new molecular markers of Treg we identified, a newtranscription factor FOXLF was discovered which may play an important role in the regulation of the "regulatory" function of those cells.