On October 4th, 2017, Drs. Jacques Dubochet (formerly of University of Lausanne in Switzerland), Joachim Frank (Columbia University), and Richard Henderson (British Medical Research Council’s Laboratory of Molecular Biology in Cambridge, UK) were awarded the Nobel Prize in Chemistry for developing cryo-electron microscopy (Cryo-EM) for the high resolution structure determination of biomolecules in solution.
BioXFEL scientists use traditional methods of crystallizing proteins paired with the unique capabilities of cutting edge X-Ray Free Electrons Lasers (XFELs) to determine protein structure. However, many proteins can be extremely difficult to crystallize. We apply creative solutions, such as, sending proteins to the International Space Station for crystallization in zero-gravity or small angle X-Ray scattering for which a crystalline sample is unnecessary. Cryo-EM offers another complementary method.
Dr. Joachim Frank and BioXFEL’s Dr. Abbas Ourmazd and his University of Wisconsin-Milwaukee team collaborated on several projects and authored joint papers (PNAS: Trajectories of the ribosome as a Brownian nanomachine and bioRxiv: Conformational Dynamics and Energy Landscapes of Ligand Binding in RyR1) which were cited in the background of the Nobel Prize award.
The Ourmazd lab, which includes Associate Professor Peter Schwander and Senior Scientist Russell Fung, has helped researchers at Frank’s lab by contributing mathematical techniques to help extract information from pictures obtained by the electron microscopy.
“We have developed a whole new way of determining the function of biomolecules responsible for keeping us alive,” said Abbas Ourmazd, distinguished professors of physics. “Simply put, we have developed a way to make 3-D movies of these ‘bio-machines’ as they perform their functions.”
Frank spoke about the partnership in a recent interview with the German newspaper Westfalenpost.
“I have a very interesting collaboration with a group in Wisconsin led by Abbas Ourmazd with the goal of analyzing thousands of molecular images undergoing continuous movements,” he was quoted as saying. “I believe this will lead cryo-EM to full ‘four-dimensional’ structure determination.”
Other researchers and BioXFEL members in the Ourmazd lab who were on one or both of the papers are Ali Dashti, Ghoncheh Mashayekhi and Ahmad Hosseinizadeh.
Ourmazd’s lab recently reconstructed a 3-D movie of a virus preparing to infect a cell from a multitude of 2-D “snapshots” taken by the XFEL at SLAC National Accelerator Laboratory.