X-ray free electron-laser based structural biology
Structural biology, and in particular scattering-based techniques making use of X-rays and electrons, have provided high-resolution insight in the structure and function of molecules, molecular assemblies, and cells. Despite a lot of advances in instrumentation, radiation damage limits high resolution imaging of biological material using conventional X-ray or electron based approaches and can change in particular redox sensitive cofactors, compromising chemical insight in reaction mechanisms. X-ray free-electron lasers (XFELs) exceed the peak brilliance of conventional synchrotrons by almost 10 billion times. They promise to break the nexus between radiation damage, sample size, and resolution by providing extremely intense femtosecond X-ray pulses that pass the sample before the onset of significant radiation damage. We explore the possibilities and limitations of XFELs for structural biology, in particular for damage free data collection as well as for time-resolved measurements. To this end, several groups within the department join forces in a comprehensive interdisciplinary approach, encompassing theory, instrumentation, data analysis, biochemistry and structural biology to create new technical capabilities and yield new scientific insight.
Our achievements include algorithm development capable of dealing with inhomogeneous samples, resulting in the first three-dimensional reconstruction of a non-crystalline aerosolized single particle, the first high resolution crystal structure determined by serial femtosecond crystallography (SFX) using microcrystals, the first demonstration of de-novo structure determination, and the first ultra-fast time-resolved SFX experiment, revealing the mechanism of how the breaking of a single covalent bond results in large structural changes on sub-picosecond time scales.