Descripción del proyecto
Una simulación basada en agentes ayudará a explicar el comportamiento de los condensados biomoleculares
Los organismos constan en gran medida de agua con numerosas biomoléculas, compuestos e iones intercalados. Dentro de las células, estos constituyentes forman distintos compartimentos que desempeñan funciones diferentes. Con frecuencia, los compartimentos grandes están envueltos por una membrana, mientras que los más pequeños se forman espontáneamente como resultado de las interacciones entre moléculas dispersas. En consecuencia, estos condensados biomoleculares se comportan de forma parecida a las gotas líquidas. Su funcionamiento incorrecto interviene en enfermedades como el Alzheimer, el Parkinson y el cáncer. El proyecto EmulSim, financiado con fondos europeos, investigará cómo las células sanas controlan sus condensados en todas las escalas dimensionales para dilucidar cómo dejan de funcionar correctamente cuando se produce una enfermedad. Esta información dará lugar a un marco nuevo de simulación basado en agentes para contribuir al desarrollo de nuevos tratamientos.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
80539 Munchen
Alemania