The spatiotemporal organization of cellular material is a marvel in physics, chemistry, and biology, with compartmentalization playing a key role in coordinating molecular functions. Over the past decade, groundbreaking research has shown that many intracellular compartments are not membrane-bound but are dynamic assemblies known as condensates, formed through liquid-liquid phase separation of biomolecules like proteins and nucleic acids. However, when these condensates are misregulated, they can form harmful solid-like aggregates, which are linked to age-related and neurodegenerative diseases.

The In-phase project aims to develop a novel computational approach to understand the dynamic behavior of molecules within functional condensates and how their misregulation leads to pathological solid aggregates. The project will create a multiscale modeling platform that integrates coarse-grained force fields with atomistic simulations to address critical questions: What molecular features in RNA and protein sequences regulate phase behavior? What causes biomolecular condensates to change their material properties over time? Can we prevent the formation of pathological aggregates caused by condensate misregulation?

The main goals of In-phase are to: (1) understand the thermodynamic and intermolecular forces that drive condensates out of their functional state, and (2) explore strategies to prevent abnormal phase transitions in RNA/protein condensates. This work is groundbreaking, as it will reveal the mechanisms by which the structure and sequence of RNA and proteins influence the material properties of intracellular condensates and their role in cellular dysfunction, providing insights into potential therapeutic interventions.