Massive Exploration of the Sequence Dependence of Protein Phase Separation

Protein solutions can spontaneously de-mix and form very concentrated droplets within a background of a very dilute solution: the concentration difference between inside and outside of the droplets can be a factor of 100 or more. This process is called liquid-liquid phase separation (LLPS) and is, for example, the mechanism behind the formation of membrane-less organelles in biology. There is great potential in both medicine and biotechnology in the ability to control this process through external parameters. However, it is currently not well understood how a given protein sequence interacts with the external parameters (pH, temperature, other compounds) to drive LLPS. Current technology allows to study this phenomenon at a relatively small scale, with ~10 different protein sequences routinely investigated. Here I propose to develop a revolutionary new methodology in order to test the LLPS behaviour of, ultimately, millions of times more different protein sequences than is currently possible.