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Computational methods and modeling to decipher organelle nanophysiology

Project description

Computational models of cell cytoplasm and organelle dynamics at nanoscale resolution

The goal of the EU-funded OrganellenanoComp project is to study the nanoscale organisation underlying physiological functions by modelling the flow of ions and molecules in the cytoplasm of neuronal and glial cells to organelles in various conditions. The proposal is based on mathematical modelling, large data analysis, simulation methods and the associated algorithms. The objective is to develop physical models of molecular diffusion and electro-diffusion relevant to nanophysiology. These models will be applied to interpret molecule or receptor transport and aggregation in some specific nano-regions. Using developed models, researchers will analyse data about single molecular motion or flux regulation inside the organelles, such as the endoplasmic reticulum or mitochondria, and calcium exchange in nano-domains during synaptic transmission in dendrites.

Objective

Neuronal and glial physiology in nanodomains remains poorly understood due to the spatio-temporal limitation of direct unperturbed in vivo measurements. Yet, it is the scale of voltage regulation, ionic, proteins and molecular trafficking, metabolism control and local signal transduction. The goal of this proposal is to determine how the flow of ions and molecules is regulated in the cytoplasm in relation with organelles, such as the endoplasmic reticulum and mitochondria in various physiological conditions such as steady-state, induction of plastic changes or ionic depletion. The approach is based on mathematical modeling, large data analysis, simulation methods, and developing the associated fast and efficient algorithms. We developed in the past 15 years computational tools such as molecular modeling, stochastic simulations and data analysis at a molecular level to study various signals such as voltage recordings or super-resolution microscopy single particle trajectories (SPTs). However, these theoretical approaches are not sufficient today to face the novel data revolution coming from SPTs, but also voltage dyes, voltage recorded by nanopipettes, or photoconversion in nanocompartments. The aim of the project is to develop physical models of molecular diffusion and electro-diffusion. These models will be applied to reconstruct and interpret the local transport, which is not homogeneous because molecules or receptors could aggregate in some specific nano-regions. We will explore the mechanisms underlying this heterogeneity. Second, we will apply these modeling and numerical simulations to analyze data about flux regulation inside the cytoplasm but also in organelles, such as the ER and mitochondria.Third we analyze calcium fluorescent data (photoactivation, local uncaging) to study how calcium is exchanged in nanodomains during synaptic transmission in dendrites and dendritic spines.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2019-ADG

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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 374 698,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 374 698,00

Beneficiaries (1)

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