Institute Jacques Monod

Paris, France

Institute Jacques Monod

Paris, France
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Wainrib G.,Stanford University | Thieullen M.,University Pierre and Marie Curie | Pakdaman K.,Institute Jacques Monod
Journal of Computational Neuroscience | Year: 2012

We introduce a method for systematically reducing the dimension of biophysically realistic neuron models with stochastic ion channels exploiting timescales separation. Based on a combination of singular perturbation methods for kinetic Markov schemes with some recent mathematical developments of the averaging method, the techniques are general and applicable to a large class of models. As an example, we derive and analyze reductions of different stochastic versions of the Hodgkin Huxley (HH) model, leading to distinct reduced models. The bifurcation analysis of one of the reduced models with the number of channels as a parameter provides new insights into some features of noisy discharge patterns, such as the bimodality of interspikeintervals distribution. Our analysis of the stochasticHH model shows that, besides being a method to reduce the number of variables of neuronal models, our reduction scheme is a powerful method for gaining understanding on the impact offluctuations due to finite size effects on the dynamics of slow fast systems. Our analysis of the reduced model reveals that decreasing the number of sodium channels in the HH model leads to a transition in the dynamics reminiscent of the Hopf bifurcation and that this transition accounts for changes in characteristics of the spike train generated by the model. Finally, we also examine the impact of these results on neuronal coding, notably, reliability of discharge times and spike latency, showing that reducing the number of channels can enhance discharge time reliability in response to weak inputs and that this phenomenon can be accounted for through the analysis of the reduced model. © Springer Science+Business Media, LLC 2011.

Meisch F.,Group of Marie Noelle Prioleau | Prioleau M.-N.,Institute Jacques Monod
Briefings in Functional Genomics | Year: 2011

The mechanisms regulating the coordinate activation of tens of thousands of replication origins in multicellular organisms remain poorly explored. Recent advances in genomics have provided valuable information about the sites at which DNA replication is initiated and the selection mechanisms of specific sites in both yeast and vertebrates. Studies in yeast have advanced to the point that it is now possible to develop convincing models for origin selection. A general model has emerged, but yeast data have also revealed an unsuspected diversity of strategies for origin positioning. We focus here on the ways in which chromatin structure may affect the formation of pre-replication complexes, a prerequisite for origin activation. We also discuss the need to exercise caution when trying to extrapolate yeast models directly to more complex vertebrate genomes. © The Author 2011. Published by Oxford University Press. All rights reserved.

Veitia R.A.,Institute Jacques Monod | Veitia R.A.,University Paris Diderot | Potier M.C.,University Pierre and Marie Curie | Potier M.C.,French National Center for Scientific Research
Trends in Biochemical Sciences | Year: 2015

Single-gene deletions, duplications, and misregulation, as well as aneuploidy, can lead to stoichiometric imbalances within macromolecular complexes and cellular networks, causing their malfunction. Such alterations can be responsible for inherited or somatic genetic disorders including Mendelian diseases, aneuploid syndromes, and cancer. We review the effects of gene dosage alterations at the transcriptomic and proteomic levels, and the various responses of the cell to counteract their effects. Furthermore, we explore several biochemical models and ideas that can provide the rationale for treatments modulating the effects of gene dosage imbalances. © 2015 Elsevier Ltd.

Ozpolat B.D.,University of Maryland University College | Ozpolat B.D.,Institute Jacques Monod | Bely A.E.,University of Maryland University College
Developmental Biology | Year: 2015

Animals that can reproduce by both asexual agametic reproduction and sexual reproduction must transmit or re-establish their germ line post-embryonically. Although such a dual reproductive mode has evolved repeatedly among animals, how asexually produced individuals establish their germ line remains poorly understood in most groups. We investigated germ line development in the annelid Pristina leidyi, a species that typically reproduces asexually by paratomic fission, intercalating a new tail and head in the middle of the body followed by splitting. We found that in fissioning individuals, gonads occur in anterior segments in the anterior-most individual as well as in new heads forming within fission zones. Homologs of the germ line/multipotency genes piwi, vasa, and nanos are expressed in the gonads, as well as in proliferative tissues including the posterior growth zone, fission zone, and regeneration blastema. In fissioning animals, certain cells on the ventral nerve cord express a homolog of piwi, are abundant near fission zones, and sometimes make contact with gonads. Such cells are typically undetectable near the blastema and posterior growth zone. Time-lapse imaging provides direct evidence that cells on the ventral nerve cord migrate preferentially towards fission zones. Our findings indicate that gonads form routinely in fissioning individuals, that a population of piwi-positive cells on the ventral nerve cord is associated with fission and gonads, and that cells resembling these piwi-positive cells migrate along the ventral nerve cord. We suggest that the piwi-positive ventral cells are germ cells that transmit the germ line across asexually produced individuals via migration along the ventral nerve cord. © 2015 Elsevier Inc.

Tanimoto H.,University of Tokyo | Tanimoto H.,Institute Jacques Monod | Sano M.,University of Tokyo
Biophysical Journal | Year: 2014

For biophysical understanding of cell motility, the relationship between mechanical force and cell migration must be uncovered, but it remains elusive. Since cells migrate at small scale in dissipative circumstances, the inertia force is negligible and all forces should cancel out. This implies that one must quantify the spatial pattern of the force instead of just the summation to elucidate the force-motion relation. Here, we introduced multipole analysis to quantify the traction stress dynamics of migrating cells. We measured the traction stress of Dictyostelium discoideum cells and investigated the lowest two moments, the force dipole and quadrupole moments, which reflect rotational and front-rear asymmetries of the stress field. We derived a simple force-motion relation in which cells migrate along the force dipole axis with a direction determined by the force quadrupole. Furthermore, as a complementary approach, we also investigated fine structures in the stress field that show front-rear asymmetric kinetics consistent with the multipole analysis. The tight force-motion relation enables us to predict cell migration only from the traction stress patterns. © 2014 by the Biophysical Society.

Davi V.,Institute Jacques Monod | Minc N.,Institute Jacques Monod
Current Opinion in Microbiology | Year: 2015

The integration of biochemical and biomechanical elements is at the heart of morphogenesis. While animal cells are relatively soft objects which shape and mechanics is mostly regulated by cytoskeletal networks, walled cells including those of plants, fungi and bacteria are encased in a rigid cell wall which resist high internal turgor pressure. How these particular mechanical properties may influence basic cellular processes, such as growth, shape and division remains poorly understood. Recent work using the model fungal cell fission yeast, Schizosaccharomyces pombe, highlights important contribution of cell mechanics to various morphogenesis processes. We envision this genetically tractable system to serve as a novel standard for the mechanobiology of walled cell. © 2015 Elsevier Ltd.

The set of these two theoretical papers offers an alternative to the hypothesis of a primordial RNA-world. The basic idea of these papers is to consider that the first prebiotic systems could have been networks of catalysed reactions encapsulated by a membrane. In order to test this hypothesis it was attempted to list the main obligatory features of living systems and see whether encapsulated biochemical networks could possibly display these features. The traits of living systems are the following: the ability they have to reproduce; the fact they possess an identity; the fact that biological events should be considered in the context of a history; the fact that living systems are able to evolve by selection of alterations of their structure and self-organization. The aim of these two papers is precisely to show that encapsulated biochemical networks can possess these properties and can be considered good candidates for the first prebiotic systems. In the present paper it is shown that if the proteinoids are not very specific catalysts and if some of the reactions of the network are autocatalytic whereas others are not, the resulting system does not reach a steady-state and tends to duplicate. In the same line, these biochemical networks possess an identity, viz. an information, defined from the probability of occurrence of these nodes. Moreover interaction of two ligands can increase, or decrease, this information. In the first case, the system is defined as emergent, in the second case it is considered integrated. Another property of living systems is that their behaviour is defined in the context of a time-arrow. For instance, they are able to sense whether the intensity of a signal is reached after an increase, or a decrease. This property can be mimicked by a simple physico-chemical system made up of the diffusion of a ligand followed by its chemical transformation catalysed by a proteinoid displaying inhibition by excess substrate. Under these conditions the system reacts differently depending on whether the same ligand concentration is reached after an increase or a decrease. © 2010 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

The present article discusses the possibility that catalysed chemical networks can evolve. Even simple enzyme-catalysed chemical reactions can display this property. The example studied is that of a two-substrate proteinoid, or enzyme, reaction displaying random binding of its substrates A and B. The fundamental property of such a system is to display either emergence or integration depending on the respective values of the probabilities that the enzyme has bound one of its substrate regardless it has bound the other substrate, or, specifically, after it has bound the other substrate. There is emergence of information if p(A)>p(AB) and p(B)>p(BA). Conversely, if p(A)

Duveau F.,Institute Jacques Monod | Felix M.-A.,Institute Jacques Monod | Felix M.-A.,Ecole Normale Superieure de Paris
PLoS Biology | Year: 2012

Robust biological systems are expected to accumulate cryptic genetic variation that does not affect the system output in standard conditions yet may play an evolutionary role once phenotypically expressed under a strong perturbation. Genetic variation that is cryptic relative to a robust trait may accumulate neutrally as it does not change the phenotype, yet it could also evolve under selection if it affects traits related to fitness in addition to its cryptic effect. Cryptic variation affecting the vulval intercellular signaling network was previously uncovered among wild isolates of Caenorhabditis elegans. Using a quantitative genetic approach, we identify a non-synonymous polymorphism of the previously uncharacterized nath-10 gene that affects the vulval phenotype when the system is sensitized with different mutations, but not in wild-type strains. nath-10 is an essential protein acetyltransferase gene and the homolog of human NAT10. The nath-10 polymorphism also presents non-cryptic effects on life history traits. The nath-10 allele carried by the N2 reference strain leads to a subtle increase in the egg laying rate and in the total number of sperm, a trait affecting the trade-off between fertility and minimal generation time in hermaphrodite individuals. We show that this allele appeared during early laboratory culture of N2, which allowed us to test whether it may have evolved under selection in this novel environment. The derived allele indeed strongly outcompetes the ancestral allele in laboratory conditions. In conclusion, we identified the molecular nature of a cryptic genetic variation and characterized its evolutionary history. These results show that cryptic genetic variation does not necessarily accumulate neutrally at the whole-organism level, but may evolve through selection for pleiotropic effects that alter fitness. In addition, cultivation in the laboratory has led to adaptive evolution of the reference strain N2 to the laboratory environment, which may modify other phenotypes of interest. © 2012 Duveau, Felix.

Todeschini A.-L.,Institute Jacques Monod | Todeschini A.-L.,University Paris Diderot | Georges A.,Institute Jacques Monod | Georges A.,University Paris Diderot | And 2 more authors.
Trends in Genetics | Year: 2014

Specific recognition of cis-regulatory regions is essential for correct gene regulation in response to developmental and environmental signals. Such DNA sequences are recognized by transcription factors (TFs) that recruit the transcriptional machinery. Achievement of specific sequence recognition is not a trivial problem; many TFs recognize similar consensus DNA-binding sites and a genome can harbor thousands of consensus or near-consensus sequences, both functional and nonfunctional. Although genomic technologies have provided large-scale snapshots of TF binding, a full understanding of the mechanistic and quantitative details of specific recognition in the context of gene regulation is lacking. Here, we explore the various ways in which TFs recognizing similar consensus sites distinguish their own targets from a large number of other sequences to ensure specific cellular responses. © 2014 Elsevier Ltd.

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