Romain Yvinec

Research Director in Mathematics

Physiologie de la Reproduction et des Comportements, INRAE UMR85, CNRS UMR7247, Université de Tours,F-37380 Nouzilly, France +33 (0) 2 47 42 76 55 romain.yvinec [at] inrae.fr BIOlogy of GPCRs Signaling Systems (BIOS) , PRC, INRAE UMR85, CNRS UMR7247, Université de Tours,F-37380 Nouzilly, France MUltiSCAle population dynamics for physiological systems (MUSCA) , EPC INRIA-INRAE-CNRS, Université Paris-Saclay, Inria, Inria Saclay-Ile-de-France, 91120, Palaiseau, France

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Currently funded projects:

• Exploratory Action INRIA Compartimentage (coord: R.Y. 2022-2024): Spatio-Temporal Imaging and Modeling of Signaling Pathway Compartmentalization
  
  

  G protein-coupled receptors (GPCRs) form a large class of membrane receptors mainly targeted by therapeutic agents. Recently, it has been demonstrated that these receptors are capable of inducing cascades of biochemical reactions from extremely dynamic pools of intracellular compartments. The subcellular trafficking of receptors thus generates a spatio-temporal heterogeneity of cell signaling, with a critical role on physiological functions, and profound consequences on the search for new therapeutic strategies. In the COMPARTIMENTAGE project, we aim to develop new modeling formalism, combining biochemical reaction networks and coagulation-fragmentation dynamics to fully represent the diversity and complexity of signaling pathways. By comparing our models with data from confocal microscopy imaging with super spatio-temporal resolution, we wish to reveal how the spatio-temporal heterogeneity of intracellular compartments conditions the response of cells to extracellular signals.
  
  
  • Post-doc position available starting November 2022, in PDE modeling, combining biochemical reaction networks and coagulation-fragmentation dynamics. Deadline for applications: 09/09/2022


• ANR Project Collaboratif de Recherche OVOPAUSE (coord: R.Y. 2022-2027): Dynamics and control of female germ cell populations: understanding aging through population dynamics models
  
  

  Female reproductive function is supported by a massive production of specialised germ cells, the oocytes. In women, as in most mammals, the stock of oocytes is established in the peri-natal period and it keeps decreasing all along life, leading to its exhaustion at menopause and to reproductive function arrest. Oocytes are surrounded by layers of somatic granulosa cells to form ovarian follicles. Different populations of follicles co-exist in the ovaries: the quiescent primordial follicles, which constitute the stock of follicles, and growing follicles. Regularly and until exhaustion, primordial follicles are recruited in the growing follicle pool, according to tightly regulated dynamics leading to either their final maturation for ovulation or to their elimination by a physiological process. Ovulation requires a tight coordination between the recruitment of an adequate number of primordial follicles and of growing follicles achieving maturation at ovulation. Accelerated exhaustion of follicles is a cause of premature ovarian failure, and disrupted growth also leads to fertility disorders. Controlling primordial and growing follicle population distribution, through the recruitment and subsequent maturation of follicles is a critical issue for fertility, which is at the heart of assisted reproductive technologies. In this context, the objectives of OVOPAUSE are 1/ to investigate to which extent primordial follicles and growing follicles establish a tight dialogue notably through endocrine/paracrine factors to ensure regular ovulations throughout reproductive life, 2/ to quantify the dynamics and nonlinear interactions at play within the follicle population and 3/ to monitor the depletion of the stock of oocytes over ageing, both before puberty and during reproductive life. Using innovative imaging approaches and artificial intelligence-based analyses, the distribution of the follicle population will be acquired in young and adult mice and medaka, two relevant animal models for reproductive biology. Experimental manipulations of these models offer the possibility of addressing these issues in both a physiological situation and in a situation where the inter-follicular dialogue is disrupted. Using population dynamics models, we will build a comprehensive modelling framework to formulate and investigate the control of follicle dynamics. We intend to faithfully reproduce follicle size and maturation distribution, quantitatively and dynamically. Statistical estimation procedures will unveil the controls behind the observed population of oocytes through ageing. A comprehensive parameter sensitivity study will shed light on potential action levers to lengthen the lifespan of the ovarian reserve. We will study in particular scenarios of preservation of the stock of ovarian follicles, which is of crucial importance in oncofertility, or of the over-representation of growing follicles, which is frequently encountered in the polycystic ovary syndrome.
  
  
  • Post-doc position available soon in stochastic and deterministic population dynamics, and image and statistical analysis using artificial intelligence. Please contact us !


• Metaprogram DIGIT-BIO IMMO (coord: Violette Thermes and R.Y. 2021-2023): Imagerie et modélisation multi-échelle pour la compréhension de la dynamique ovarienne chez le poisson

  

  The IMMO project proposes to exploit new 3D imaging and Artificial Intelligence methods to visualize and count all the oocytes in fish ovaries at different ages, in order to describe exhaustively and quantitatively the entire population of oocytes and ovarian follicles. These data will be used to validate a mathematical model describing follicular dynamics and their controls on fish lifespan, which will reveal information inaccessible from data alone. The model simulations will reproduce the different types of disturbances affecting oogenesis.





• Metaprogram DIGIT-BIO IMAGO (coord: Frédéric Jean-Alphonse and Béatrice Laroche 2022-2024): Imagerie et modélisation des dynamiques spatio-temporelles de la signalisation et du trafic des récepteurs couplés aux protéines G (RCPG)
  The IMAGO project proposes to revisit GPCR signaling models, based on the recent demonstration that these receptors transduce signaling mechanisms not only from the plasma membrane, but also from different intracellular compartments. By mobilizing several single cell imaging techniques, we will establish the spatial and dynamic map of receptor trafficking. This information will then be confronted with localized measurements of the main effector molecules of the receptors, thanks to the use of fluorescent biosensors targeted selectively in various cellular domains of interest. Through mathematical and statistical analysis approaches, these data will reveal spatio-temporal signaling information which will then be integrated into a spatialized dynamic model (of the reaction-advection-diffusion type) of GPCR signaling. This work will make it possible to question the global impact of the sub-cellular spatialization of GPCR signaling. We will work on receptors of interest in the physiology of reproduction, which may lead to revisiting traditional pharmacological approaches to controlling reproduction, which only target receptors located at the plasma membrane. We will strive to draw generic conclusions useful to the signaling network community.


• ANSES PNR EST GinFiz (coord: Rémy beaudouin 2020-2024): Gonadal aromatase inhibition and other toxicity pathways leading to Fecundity Inhibition in Zebrafish: from initiating events to population impacts
  The GinFiz project aims to develop and test new methods to characterize the unintended effects of phytopharmaceuticals products on fish populations, in particular the impacts resulting from damage to the endocrine system of individuals. The overall objective of this project will be the development and improvement of a qAOP leading to a decrease in fertility in order to accurately predict the impacts of Endocrine Disruptors on the different biological levels (from the internal doses accumulated to the effects on populations ).

Past projects:

• Crédit Incitatifs Phase (2020-2021): DYNAGO, vers une biologie systémique multi-échelle : intégration du réseau de signalisation FSH dans un modèle multi-échelle de la folliculogenèse
• Crédit Incitatifs Phase (2018-2019): MSBFOLLICULO, vers une biologie systémique multi-échelle : intégration du réseau de signalisation FSH dans un modèle multi-échelle de la folliculogenèse
• Financement Agreenium pour un cours doctoral (2018) : Modélisation de systèmes dynamiques en agronomie, écologie et biologie moléculaire
• Actions de Recherches Collaboratives Universités de Tours et de Poitiers (2016) : Modélisation stochastique et analyse statistique en expression génétique
• Crédit Incitatifs Phase 2016 : TRADUCTOPHENO, prédire le phénotype cellulaire à la lumière du traductome