Description du projet
Une simulation fondée sur des agents aidera à expliquer le comportement des condensats biomoléculaires
Les organismes sont en grande partie constitués d’eau, avec de nombreuses biomolécules, composés et ions intercalés. À l’intérieur des cellules, ces constituants forment différents compartiments qui remplissent des fonctions. Si les grands compartiments sont souvent entourés d’une membrane, la plupart des petits compartiments se forment spontanément à partir des interactions entre les molécules dispersées. Par conséquent, ces condensats biomoléculaires se comportent comme des gouttelettes de liquide. Leur dysfonctionnement est impliqué dans des maladies, notamment la maladie d’Alzheimer, la maladie de Parkinson et le cancer. Le projet EmulSim, financé par l’UE, étudiera comment les cellules saines contrôlent leurs condensats à toutes les échelles de longueur afin d’élucider comment ils deviennent dysfonctionnels dans les états pathologiques. Les connaissances acquises permettront de mettre au point un nouveau cadre de simulation fondé sur des agents qui permettra de soutenir le développement de nouveaux traitements.
Objectif
Biological cells consist of a myriad of interacting biomolecules that collectively arrange in stable structures. For example, molecules undergo phase separation to form so-called biomolecular condensates. We now know that malfunctioning condensates can cause diseases like Alzheimer’s, Parkinson’s, and cancer. Yet, we do not understand how condensates become malfunctioning and how healthy cells control them. Some challenges in understanding condensate dynamics are that cells are heterogeneous, have complex material properties, and exhibit significant thermal fluctuations. Biological cells are also alive and use fuel molecules to control processes actively. I recently showed that active chemical reactions could generally affect the dynamics of droplets. However, it is unclear how such active droplets behave in the complex environments inside cells.
EmulSim will study how cells control biomolecular condensates and provide a novel integrated simulation method incorporating relevant processes on all length scales. On the scale of individual droplets, I will investigate the influence of driven reactions and elastic material properties of droplets. On the cellular scale, I will study the effect of the elastic cytoskeleton and the presence of multiple compartments. For each of these processes, I will derive experimentally verified models using examples of relevant biological processes, including cell division, chromatin organization, and signaling. Combining the physical theories for these critical processes will culminate in an agent-based model describing a collection of droplets, ultimately also including number fluctuations. This novel simulation framework will model biomolecular condensates in their cellular environment. Taken together, EmulSim will propel our understanding of biomolecular condensates and lay the ground for the development of novel therapies in medicine.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
80539 Munchen
Allemagne