Multiscale Computational Immunology

We are developing multiscale modelling approaches to decipher biophysical mechanisms involved in immune response from pathogen-host cell interactions to immune cells adaptation to their environment. We are especially interested to understand, from the nano- to the micro- scale, the restructuration of membrane constituents occurring during these immunological processes.

Multi-scale molecular dynamics simulations can be seen as a computational microscope to probe the dynamics of membrane systems from nanometers to a micrometer.

Our team uses a broad range of modeling approaches (from homology modelling to docking and Molecular Dynamics simulations) to understand biophysical properties of membrane components (lipids and proteins) of immune cells and pathogens (see bellow). We are also developing multiscale workflows to integrate heterogeneous experimental data into our models.  

Mycobacterial lipids and their action on host membranes
Mycobacterium tuberculosis (Mtb) is the main causative agent of the disease Tuberculosis (TB). These bacteria are known for their complex lipids. These lipids can be used as virulence effectors acting at the host membrane to damage it and modulate immune response. They are also the building blocks of a very thick and tight envelope which constitute a diffusion barrier to drugs, thus contributing to Mtb persistence. We are designing atomistic and coarse grain models of these lipids and study their biophysical properties in different membrane environments to better understand their functions and assemblies.

Membrane proteins involved in immune response: from dimer to supramolecular assemblies
Immunological processes can involve large-scale spatial reorganization of receptors and membrane proteins at the surface of immune cells and pathogens. To understand these phenomena, we are developing multiscale approaches to model membrane proteins and their interactions from simple dimer to large supramolecular assemblies comprising hundreds of proteins.

Membrane remodeling up to the microscale
Immune cells membrane can undergo large remodeling. We are applying molecular dynamics simulations and mesoscale models (in collaboration with Pr Destainville, IRSAMC, Toulouse) to probe the biophysical changes of the cell membranes from the fission/fusion processes at the nanoscale up to the creation of large organelles such as phagosome.

Computational design of new immuno-modulators and antimicrobial molecules
Understanding the biophysical processes implicating membrane components of immune cells and pathogens help us developing new molecules that can modulate immune response or act as antimicrobial agent. These new molecules are computationally designed to customize their structures and functions.

Team members

Research Scientist

Matthieu Chavent (CNRS)

Postdoctoral Fellow

Adrien Schahl

Augenstreich et al. (2019) The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages. Proc Natl Acad Sci USA

Chavent et al. (2018) Interactions of the EphA2 kinase domain with PIPs in membranes: Implications for receptor function. Structure

Chavent et al. (2018) How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins. Nat Commun

Jackson et al. (2016) Super-complexes of adhesion GPCRs and neural guidance receptors. Nat Commun

Chavent et al. (2016) Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale. Curr Opin Struct Biol

Rassam et al. (2015) Supramolecular assemblies underpin turnover of outer membrane proteins in bacteria. Nature

Flows of lipid at the surface of a vesicle model © M Chavent