Multi-scale modeling

Multi-scale modeling

Main leader: Romain Yvinec

What are the physiological consequences of GPCR signaling? In vivo impact and multi-scale modeling

BIOS aims to understand how signaling processes impact the effects observed at the tissue and organism level on reproduction or in social behaviors. For this, BIOS measures the effects of the in vivo administration of ligands, including antibody fragments, with different pharmacological profiles (biased ligands, allosteric modulators, intracellular signaling) and aims to link the effects of a pathway specific signaling with the functional effects sought in vivo. To do this, BIOS integrates all the data generated by the team through multi-scale modeling with mathematical and artificial intelligence approaches.

For female reproduction, work in this area is carried out in conjunction with the objectives and approaches pursued by the EPC MUSCA. Deterministic and stochastic multi-scale modeling approaches are used to represent cellular and tissue population dynamics, and are combined with innovative imaging methods and artificial intelligence image analysis methods. BIOS aims for a methodological breakthrough in the field of female reproduction, moving from fragmentary and static “snapshots” to a dynamic and integrative vision of ovarian function. BIOS is particularly interested in how to modulate gonadotropin receptor signaling to control and predict the behavior of the reproductive system, notably via the molecular dialogues involved in the proliferation and differentiation of somatic cells which underlie the maturation of 'a female gamete within an ovarian follicle. More broadly, BIOS studies the role of autocrine and endocrine regulations on the dynamics of the entire population of ovarian follicles to ensure the maintenance of regular ovulation throughout reproductive life.

The team's work on the development of antibody fragments targeting the FSHR and LHR receptors has applications in human reproduction, particularly in understanding the mechanisms of human infertility and in contraception. Only the careful characterization and at different scales of these new ligands in accordance with the team's strategy will make it possible to fulfill the specifications for the design of new non-hormonal contraceptive agents (reversibility, maintenance of menstrual cycles, without accumulation in the 'environment). Potential applications of antibody fragments are also envisaged in the areas of male contraception and in the treatment of polycystic ovarian syndromes. These antibody fragments used in breeding would make it possible to synchronize female ovulations while reducing hormonal inputs. In addition, methodological tools in this axis are developed to allow the identification of precise markers to monitor the ovarian status of individuals during the different stages of their life cycle, to quantify precise stages of folliculogenesis by artificial intelligence and to develop very sensitive dosages of the hormones LH and FSH.

For social behavior, BIOS uses the same approach combining data obtained in the team with multi-scale modeling to modulate the activity of OTR receptors and identify the molecular substrates of sociability in different models and social species (sheep , quail, mouse, man). This fundamental work has potential applications in breeding, with the identification of molecular levers for the well-being of farmed animals, deficits in social interaction being one of the first behavioral signs of affected well-being of social animals. They also have applications in human health, with the identification of new therapeutic targets for the treatment of sociability disorders, such as autism, and the consequences of social isolation. In this sense, the team is particularly interested in the identification of GPCRs, such as the OTR receptor, and their signaling networks in order to develop adapted strategies. The characterization of ligands, in particular antibody fragments, targeting this receptor has started in the team, in particular thanks to the development of the 'Live Mouse Tracker', allowing the automated and simultaneous measurement of multiple parameters of social behavior.

List of fundings:

2022-2027 ANR OVOPAUSE project, Romain Yvinec, 2 academic partner, coordinator. See the page on the Musca website
2021-2022 DIGIT-BIO INRAE ​​metaprogram, IMMO project, Romain Yvinec, 1 academic partner, co-leader.
2011-2015 ANR GPCRnet project

Team people involved:
PhD students: Louis Fostier
Postdocs: Maya Haj-Hassan, Lucas Court
Researchers: Romain Yvinec, Pascale Crépieux, Eric Reiter, Anne Poupon, Pascale Crépieux, Romain Yvinec, Frédéric Jean-Alphonse, Lucie Pellissier, Misbah Razzaq, Nicolas Azzopardi

Scientific communities: MUSCA, RT MathSAV, IRN GPCRnet, COST ERNEST, GDR Reproscience

Modification date: 13 February 2024 | Publication date: 17 September 2021 | By: CG