Molecular biophysics of disordered protein dynamics and interactions
Intrinsically disordered proteins (IDPs), and proteins containing intrinsically disordered regions (IDRs), are widespread across the eukaryotic proteome. They play key roles in a wide range of biological processes essential for maintaining normal cellular physiology and are implicated in numerous pathologies, including cancer and neurodegenerative diseases. Unlike their structured counterparts, disordered proteins typically do not necessarily require a stable and well-defined conformation for molecular recognition or functional specificity. Notably, they often contribute to the phase separation-driven assembly of various cellular condensates, such as stress granules, P-bodies and nucleoli.
We focus on the molecular-level understanding of the behavior of disordered proteins, with a particular emphasis on their interactions with nucleic acid (RNA, DNA) and protein partners, and how these interactions drive a wide spectrum of cellular functions.
The key expertise of the group is centered on single-molecule spectroscopy in combination with Förster resonance energy transfer (single-molecule FRET), both in vitro and in live cells. In addition we use a variety of other state-of-the-art biochemical and biophysical techniques, such as biomolecular nuclear magnetic resonance (NMR) spectroscopy, surface plasmon resonance (SPR), biolayer interferometry (BLI), isothermal titration calorimetry (ITC), live-cell imaging and molecular simulations, with a goal of revealing the molecular basis of their specific function.
Our current research centers on two main areas:
- exploring the behavior and interactions of disordered translation initiation factors and uncovering the mechanistic principles underlying their roles in eukaryotic translation;
- investigating the self-association properties and condensation mechanisms of these disordered factors, to elucidate their contributions to the cellular stress response and the formation of biomolecular condensates.