Project R-15236

Integrating Coarse‐Grained Molecular Dynamics and Fluorescence Spectroscopy to Unravel Disordered Protein Condensates (Research)

Biomolecular condensates are cellular structures that spontaneously form via phase separation and have attracted increasing interest in recent years. They are crucial for healthy cellular function, but are also implicated in diseases. This project focusses on understanding the condensation process of the Tau protein, which is associated with neurodegenerative diseases such as Alzheimer's disease. Presently, the physicochemical principles governing condensate formation and the mechanisms occurring within them remain elusive as current experimental techniques provide limited qualitative insights due to the complex nature of condensates. To address this gap, I will employ coarse-grained molecular dynamics simulations to model condensates. By integrating in vitro fluorescence spectroscopy data, I aim to refine the computational models and ensure their realism. The novel-inkind experiment-guided computational framework will enable me to simulate Tau and other intrinsically disordered proteins on different scales and carry out in silico experiments. Through this, I will gain comprehensive insights into the structure and dynamics of biomolecular condensation and the proteins that constitute them. This synergistic approach will advance our understanding of biomolecular condensation phenomena and their implications in Tau-related pathologies, but it can also inspire new‐generation synthetic biology, drug development and drug discovery.

01 November 2024 - 31 October 2028