In the last several years, UWM physicists have participated in experiments to capture images of atomic biology unfolding by using an X-ray free electron laser, equipment that creates slow-motion movies of molecular events happening at split-second timescales.
Already, a team led by UWM physics professor Marius Schmidt has used the XFEL at the SLAC National Accelerator Laboratory in California to image the bacterium that causes tuberculosis as it disarms an antibiotic.
Now Schmidt and his graduate students are co-authors on a paper detailing the first test of Europe’s next-generation XFEL in Hamburg, Germany, which is an order of magnitude faster than the billionth-of-a-second image-taking capability of SLAC’s XFEL.
At the inaugural testing of Europe’s XFEL in September 2017, Schmidt, doctoral student Suraj Pandey and post-doctoral researcher Christopher Kupitz joined an international research group in the imaging a bacterial enzyme that plays an important role in antibiotic resistance.
The results of the experiment were announced today by the European XFEL, the German Electron Synchrotron and the Paul Scherrer Institute in Switzerland. The team proved the speed and accuracy of the apparatus while also revealing the structural changes of an enzyme as it rendered an antibiotic useless.
By tracking the rearrangement of the atoms in the tiniest units of life, researchers can reveal how the proteins and their enzymes work – or don’t. That’s important because proteins figure prominently in the development of disease and they are the main targets of new drug compounds.
In the past, proteins have been notoriously difficult to image. One problem is they function at rates of a billionth of a billionth of a second. The speed of the camera on the European XFEL promises to be its major advantage becauseexperiments that used to take hours can now be done in a few minutes.
The XFEL produces incredibly intense X-rays in extremely short pulses that hit a crystal containing millions of proteins, a method called X-ray crystallography.
When a crystal is hit by X-rays, the rays scatter in patterns that are unique to molecules, encoding its atomic structure. The rapid-fire laser pulses result in two-dimensional snapshots of each pattern from hundreds of thousands of orientations.
The new XFEL breaks records for both its high pulse-repetition rate and the speed of its camera. It can deliver X-ray pulses every 220 nanoseconds, compared to the next-fastest rate of 8 million nanoseconds. Pairing it with one of the fastest cameras in the world – the adaptive gain integrating pixel detector – ensures that enough 2D images can be taken to mathematically reconstruct moving 3D images.
For the European XFEL experiment, UWM’s Kupitz, now a scientist at SLAC, prepared microcrystals of biological samples and brought them to Germany for measurement. Pandey, who was involved in the data analysis, was actually the first one to see the shift in electron density that signaled a task was happening.
“During the experiment, I was working on the collected data, and fortunately I was able to obtain the results which gave the highest resolution for the beta-lactamase (an enzyme produced by bacteria),” said Pandey. “I really felt accomplished. I felt that even in such a large group, I was able to contribute something important and do something to make a name for UWM.”