On a molecular level, all biological processes are carried out by proteins. Membrane proteins act as pumps and gates in the cell membrane, thus controlling all traffic that enters and leaves the cell. Because of this, they are important targets for medicine while their malfunctioning is at the heart of a plethora of diseases. But despite their enormous importance, membrane proteins are poorly understood as they are notoriously difficult to study using traditional methods based on X-rays. The more recently developed method of cryo-electron microscopy has revealed the structures of some of these proteins, but as it requires the sample to be frozen the obtained images are inherently static.
Now imagine that we could have an instrument that allows making movies of such proteins, so we can see exactly how they work and, also, why sometimes they do not work. Such a tool could revolutionize biochemistry, giving a unique insight in the structure-function relationship of nature’s molecular machinery, and helping scientists to understand membrane-protein-related diseases.
To make these molecular movies, I use a unique source that produces ultrashort flashes of electrons. Each of these flashes takes a snapshot of the protein, and together these snapshots form a molecular movie of the conformational change of the protein. To resolve the protein at high resolution while limiting radiation damage, the snapshots are taken in the form of diffraction patterns from 2D protein crystals. For this to work, the wave nature of the electrons needs to be very pronounced, i.e. the electron bunch needs a good coherence. To obtain such high-quality electron bunches, I use a unique approach: in a vacuum, Rubidium atoms are first laser-cooled to almost absolute zero temperature and then carefully ionized with a femtosecond laser pulse. The thus produced ultracold electron bunches are sufficiently coherent to create diffraction patterns from the protein crystal. In summary, by combining principles from fundamental physics with state-of-the-art technology and biochemistry, I aim to deliver a proof of concept that on the long term will advance medicine and other research fields through an improved understanding of membrane proteins.
