Mots-Clés

single cell data, C++, multiscale model, gene regulatory network

Description

About the project. A postdoctoral position is open in the Inria Dracula team. The position is to be funded by an ANR grant (MEMOIRE project). The position is an opportunity to be involved in a strongly interdisciplinary consortium, and to strengthen experience in computational biology by working on single cell data modeling. The MEMOIRE consortium previously introduced a multi-scale model of the CD8+ T cell immune response based on the description and dynamical interactions of a CD8+ T cell dynamics model and a model for a Gene Regulatory Network (Gao et al, 2016; Girel et al, 2019; Prokopiou et al, 2014). This allowed to explore the limits of the existing tools, which we aim at overcoming in the present project.

A generic multi-agent multi-scale C++ simulation framework, SiMuScale, has been developed in the Dracula team. It models both intra- and extra-cellular processes at different time scales. Its decoupled architecture allows for an easy and parsimonious extension of the model with e.g. a new kind of intra-cellular formalism. The aim of the post-doctoral position is

1st/ to implement in C++ a SiMuScale-compatible plug-in for simulating a GRN described by a piecewise deterministic Markov model (Herbach et al, 2017), and
2nd/ to couple the GRN with an existing cell dynamics model in order to
3rd/ use the multiscale model to describe experimental data and to investigate the dynamics of CD8+ T cells at the single-cell level.

Dr. Olivier Gandrillon and Dr. Fabien Crauste will co-supervise the postdoc, they have a jointly experience of interdisciplinary works and have already co-supervised several postdocs on computational immunology-related projects.

About you. The applicant will have an experience in computational biology and will be able to implement new and existing C++ codes. It should be able to share its code through Git, and to use High Performance Computing facilities. In addition, the usage of various (deterministic, stochastic) mathematical formalisms and an experience in parameter estimation with experimental data will be considered as a plus. Interdisciplinary meetings and research are at the core of the project, so it is expected that the Postdoc Fellow is confortable with researchers from other fields. Good ability for team playing will be appreciated.

References:
Gao, Arpin, Marvel, Prokopiou, Gandrillon, Crauste (2016) IL-2 sensitivity and exogenous IL-2 concentration gradient tune the productive contact duration of CD8+ T cell-APC: a multiscale modeling study. BMC Systems Biology 10, 77. 
Girel, Arpin, Marvel, Gandrillon, Crauste (2019) Model-based assessment of the role of uneven partitioning of molecular content on heterogeneity and regulation of differentiation in CD8 T-cell immune responses. Front. Immunol. 10, 230.
Herbach, Bonnaffoux, Espinasse, Gandrillon (2017). Inferring gene regulatory networks from single-cell data: a mechanistic approach. BMC Systems Biology 11:105.
Prokopiou, Barbarroux, Bernard, Mafille, Leverrier, Arpin, Marvel, Gandrillon, Crauste (2014) Multiscale modeling of the early CD8 T cell immune response in lymph nodes: an integrative study. Computation, 2(4), 159-181.