11 results on '"Lemarre, Paul"'
Search Results
2. Generalizing a mathematical model of prion aggregation allows strain coexistence and co-stability by including a novel misfolded species
- Author
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Lemarre, Paul, Pujo-Menjouet, Laurent, and Sindi, Suzanne S
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Biochemistry and Cell Biology ,Biological Sciences ,Rare Diseases ,Emerging Infectious Diseases ,Infectious Diseases ,Neurodegenerative ,Transmissible Spongiform Encephalopathy (TSE) ,Brain Disorders ,Neurosciences ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Animals ,Computational Biology ,Computer Simulation ,Humans ,Kinetics ,Mathematical Concepts ,Models ,Biological ,Models ,Molecular ,Phenotype ,Prion Diseases ,Prions ,Protein Aggregation ,Pathological ,Protein Conformation ,Protein Folding ,Protein Stability ,Proteostasis Deficiencies ,Coexistence ,Nucleated polymerization ,Protein aggregation ,Protein misfolding ,Strains ,Subunits ,Mathematical Sciences ,Bioinformatics ,Biological sciences ,Mathematical sciences - Abstract
Prions are proteins capable of adopting misfolded conformations and transmitting these conformations to other normally folded proteins. Prions are most commonly known for causing fatal neurodegenerative diseases in mammals but are also associated with several harmless phenotypes in yeast. A distinct feature of prion propagation is the existence of different phenotypical variants, called strains. It is widely accepted that these strains correspond to different conformational states of the protein, but the mechanisms driving their interactions remain poorly understood. This study uses mathematical modeling to provide insight into this problem. We show that the classical model of prion dynamics allows at most one conformational strain to stably propagate. In order to conform to biological observations of strain coexistence and co-stability, we develop an extension of the classical model by introducing a novel prion species consistent with biological studies. Qualitative analysis of this model reveals a new variety of behavior. Indeed, it allows for stable coexistence of different strains in a wide parameter range, and it also introduces intricate initial condition dependency. These new behaviors are consistent with experimental observations of prions in both mammals and yeast. As such, our model provides a valuable tool for investigating the underlying mechanisms of prion propagation and the link between prion strains and strain specific phenotypes. The consideration of a novel prion species brings a change in perspective on prion biology and we use our model to generate hypotheses about prion infectivity.
- Published
- 2019
3. Modeling the spatial propagation of Aβ oligomers in Alzheimer’s Disease
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Andrade-Restrepo Martin, Lemarre Paul, Pujo-Menjouet Laurent, Tine Leon Matar, and Ciuperca Sorin Ionel
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Applied mathematics. Quantitative methods ,T57-57.97 ,Mathematics ,QA1-939 - Abstract
Recent advances in the study of Alzheimer’s Disease and the role of Aβ amyloid formation have caused the focus of biologists to progressively shift towards the smaller protein assemblies, the oligomers. These appear very early on in the disease progression and they seem to be the most infectious species for the neurons. We suggest a model of spatial propagation of Aβ oligomers in the vicinity of a few neurons, without considering the formation of large fibrils or plaques. We also include a simple representation of the oligomers neurotoxic effect. A numerical study reveals that the oligomers spatial dynamics are very sensitive to the balance between their diffusion and their replication, and that the outcome in terms of the progression of AD strongly depends on it.
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- 2020
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4. A reaction–diffusion model of spatial propagation of Aβ oligomers in early stage Alzheimer’s disease
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Andrade-Restrepo, Martin, Ciuperca, Ionel Sorin, Lemarre, Paul, Pujo-Menjouet, Laurent, and Tine, Léon Matar
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- 2021
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5. Le prion sous toutes ses formes - Modélisation mathématique des processus d’agrégation et de conversion des protéines
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Lemarre, Paul, STAR, ABES, Institut Camille Jordan (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Modélisation mathématique, calcul scientifique (MMCS), Institut Camille Jordan, Université Claude Bernard Lyon 1, France, Laurent Pujo-Menjouet, and Suzanne Sindi
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Modèle cinétique ,Dynamical systems ,[MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP] ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Protein aggregation ,Kinetic model ,Systèmes dynamiques ,[MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP] ,Équations différentielles ordinaires ,Agrégats de protéines ,Ordinary differential equations - Abstract
Following the discovery that prions are self-replicating assemblies of proteins, mathematical models were developed in parallel with experimental methods in order to conceptualize this phenomenon. After four decades of research, much insight has been gained into protein misfolding processes and the neurodegenerative diseases which they cause. However, the complexity of these systems remains undiminished and the classical models of protein aggregation are now showing their limits. In particular, the observed spectrum of objects generated during the propagation of prions is not accounted for in any model, whereas it keeps expanding under the development of experimental tools.In the present manuscript, our aim is to identify the weaknesses of classical models of prion propagation in light of recent biological evidence. We then suggest modified and improved models, by including different processes, by adding more levels of organization and more diversity to protein aggregates. Three main topics are presented, corresponding to different instances of protein aggregation and different biological systems. The first part takes place in the mammalian nervous system, and investigates the self-aggregation kinetics of PrP, the aptly named prion protein. In the second part, we model the replication of protein aggregates inside dividing yeast cells, by proposing a novel multi-scale approach. In the third part, we explore the spatial propagation of small protein oligomers in the early stages of Alzheimer’s Disease. These three axes are linked by the central role of structural diversity in the global protein aggregation system., Depuis la découverte de la nature des prions, de nombreux modèles mathématiques ont été proposés afin de représenter ces assemblages de protéines et leur réplication. Après quatre décennies de recherche expérimentale et conceptuelle, la compréhension des phénomènes d’agrégation de protéines, ansi que des maladies neurodégénératives qui leurs sont associées, a grandement progressé. Cependant la complexité de ces systèmes reste entière, et les modèles classiques commencent à montrer leurs limites. En particulier, aucun modèle ne reproduit l’immense diversité des objets qui sont observés au cours de la propagation des prions, alors que l’on en découvre continuellement de nouveaux sous l’avancée des procédés expérimentaux. Dans ce manuscrit, notre objectif est d’identifier les faiblesses des modèles classiques à travers l’apport de résultats biologiques récents. Par la suite, nous proposons des améliorations à ces modèles en incluant de nouveaux processus, en ajoutant des niveaux de structuration et de diversité aux agrégats. Trois axes orientent les résultats, correspondant à trois contextes biologiques différents. La première partie se déroule dans le système nerveux des mammifères, et étudie la cinétique d’auto-agrégation de PrP, la bien nommée protéine prion. Dans la seconde partie nous abordons une approche multi-échelle novatrice pour représenter la propagation d’agrégats de protéines dans des cellules de levure en croissance. La troisième partie explore la dissémination spatiale de petits oligomères dans les étapes précoces de la maladie d’Alzheimer. Ces trois axes se recoupent autour du thème central de la diversité structurale et son rôle crucial dans la propagation.
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- 2021
6. A reaction–diffusion model of spatial propagation of A$$\beta $$ oligomers in early stage Alzheimer’s disease
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Andrade-Restrepo, Martin, primary, Ciuperca, Ionel Sorin, additional, Lemarre, Paul, additional, Pujo-Menjouet, Laurent, additional, and Tine, Léon Matar, additional
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- 2021
- Full Text
- View/download PDF
7. A unifying model for the propagation of prion proteins in yeast brings insight into the [PSI+] prion
- Author
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Lemarre, Paul, primary, Pujo-Menjouet, Laurent, additional, and Sindi, Suzanne S., additional
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- 2020
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8. Modeling the spatial propagation of Aβ oligomers in Alzheimer's Disease.
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Calvez, Vincent, Grandmont, Céline, Lochërbach, Eva, Poignard, Clair, Ribot, Magali, Vauchelet, Nicolas, Andrade-Restrepo, Martin, Lemarre, Paul, Pujo-Menjouet, Laurent, Tine, Leon Matar, and Ciuperca, Sorin Ionel
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ALZHEIMER'S disease ,AMYLOID beta-protein precursor ,OLIGOMERS ,NEUROTOXICOLOGY ,DISEASE progression ,COMPUTER simulation of biological systems - Abstract
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- 2020
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9. Modeling the spatial propagation of Aβ oligomers in alzheimer's disease
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Andrade-Restrepo, Martín, Lemarre, Paul, Pujo-Menjouet, Laurent, Tine, Leon, Ciuperca, Sorin, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique, calcul scientifique (MMCS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan [Villeurbanne] (ICJ), Pujo-Menjouet, Laurent, Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ)
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[MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS] ,[MATH.MATH-DS] Mathematics [math]/Dynamical Systems [math.DS] ,[MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP] ,[MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2018
10. A unifying model for the propagation of prion proteins in yeast brings insight into the [PSI+] prion.
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Lemarre, Paul, Pujo-Menjouet, Laurent, and Sindi, Suzanne S.
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PRIONS , *IMPULSIVE differential equations , *CHEMICAL processes , *YEAST , *GUANIDINIUM chlorides - Abstract
The use of yeast systems to study the propagation of prions and amyloids has emerged as a crucial aspect of the global endeavor to understand those mechanisms. Yeast prion systems are intrinsically multi-scale: the molecular chemical processes are indeed coupled to the cellular processes of cell growth and division to influence phenotypical traits, observable at the scale of colonies. We introduce a novel modeling framework to tackle this difficulty using impulsive differential equations. We apply this approach to the [PSI+] yeast prion, which is associated with the misconformation and aggregation of Sup35. We build a model that reproduces and unifies previously conflicting experimental observations on [PSI+] and thus sheds light onto characteristics of the intracellular molecular processes driving aggregate replication. In particular our model uncovers a kinetic barrier for aggregate replication at low densities, meaning the change between prion or prion-free phenotype is a bi-stable transition. This result is based on the study of prion curing experiments, as well as the phenomenon of colony sectoring, a phenotype which is often ignored in experimental assays and has never been modeled. Furthermore, our results provide further insight into the effect of guanidine hydrochloride (GdnHCl) on Sup35 aggregates. To qualitatively reproduce the GdnHCl curing experiment, aggregate replication must not be completely inhibited, which suggests the existence of a mechanism different than Hsp104-mediated fragmentation. Those results are promising for further development of the [PSI+] model, but also for extending the use of this novel framework to other yeast prion or amyloid systems. Author summary: In the study of yeast prions, mathematical modeling is a powerful tool, in particular when it comes to facing the difficulties of multi-scale systems. In this study, we introduce a mathematical framework for investigating this problem in a unifying way. We focus on the yeast prion [PSI+] and present a simple molecular scheme for prion replication and a model of yeast budding. In order to qualitatively reproduce experiments, we need to introduce a non-linear mechanism in the molecular rates. This transforms the intracellular system into a bi-stable switch and allows for curing to occur, which is a crucial phenomenon for the study of yeast prions. To the best of our knowledge, no model in the literature includes such a mechanism, at least not explicitly. We also describe the GdnHCl curing experiment, and the propagon counting procedure. Reproducing this result requires challenging hypotheses that are commonly accepted, and our interpretation gives a new perspective on the concept of propagon. This study may be considered as a good example of how mathematical modeling can bring valuable insight into biological concepts and observations. [ABSTRACT FROM AUTHOR]
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- 2020
- Full Text
- View/download PDF
11. Generalizing a mathematical model of prion aggregation allows strain coexistence and co-stability by including a novel misfolded species
- Author
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Lemarre, Paul, primary, Pujo-Menjouet, Laurent, additional, and Sindi, Suzanne S., additional
- Published
- 2018
- Full Text
- View/download PDF
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