RESEARCH AREA III
TUNING STABILITY AND HOMOGENEITY
Formulations denote the active molecules, such as chemical entities or biomolecules, together with their liquid environment. While formulations do increase the functionality and bioavailability of active molecules, their long-lasting stability is often compromised by phase changes, such as crystallization, liquid-liquid phase separation (LLPS) or denaturation.
Drawing on the remarkable influence of the liquid environment, RESOLV will design highly stable formulations while maintaining the functionality of the active molecules. To realize this goal, we will engineer customized liquid environments boosting the solubility and kinetic stability of active molecules, akin to Area II. RESOLV will increase the applicability of hydrophobic pharmaceuticals by crafting customized mesophase structures to overcome the limitations of low aqueous solubility and thus bioavailability.
In nature, cells can be viewed as formulations of biomolecules, such as enzymes. A major goal of RESOLV is to uncover the mechanism by which enzymes become more active in the distinct solvent environment of liquid condensates induced by LLPS.
The THz methodology, pioneered by RESOLV, to probe local hydration changes at interfaces in Area I will be key to developing a novel Micro-THz calorimetry-microscope to map local hydration changes and LLPS even in living cells. Uncovering how local hydration changes regulate LLPS in cells will guide pathways to prevent liquid condensates from turning into toxic aggregates.