What's Happening?
Four researchers, including Guido Meier from the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg, have been awarded an ERC Synergy Grant of approximately €9.2 million over
six years. The team, which also includes Thomas J. Lane from Deutsches Elektronen-Synchrotron (DESY), Doeke Hekstra from Harvard University, and John Beale from the Paul Scherrer Institute PSI, will develop a new method to investigate how proteins respond to electric fields. This research aims to trigger protein dynamics using electric fields, rather than traditional laser pulses, to better mimic conditions found in living organisms. Their project, SPARX (Structural Perturbations by Applied electRic-field Xtallography), will build on established serial crystallography techniques and electric-field crystallography. The goal is to observe proteins in action at facilities like the X-ray free-electron laser SwissFEL, with Meier's team developing precision electronics to deliver fast, well-defined electric field pulses to protein crystals.
Why It's Important?
This research is significant because understanding protein function and reaction to stimuli is crucial for pharmaceutical research. By using electric fields to trigger protein dynamics, the researchers can investigate a broader range of proteins, including those that do not respond to light and are currently considered 'undruggable.' This new method could reveal 'cryptic binding pockets' that emerge during protein dynamics, offering novel docking sites for new therapeutics. Such discoveries could lead to the development of future treatments for serious conditions like cancer and neurological disorders, including Parkinson's disease. The project also aims to establish infrastructure that can be replicated at other synchrotron light sources worldwide, potentially accelerating drug discovery and protein research globally.
What's Next?
Over the next six years, the research team will focus on developing and testing devices that integrate electric fields into existing serial crystallography techniques. Guido Meier's team at MPSD will be responsible for designing and building prototypes of precision electronics capable of delivering electric fields exceeding 10 million volts per meter for at least 10 nanoseconds to protein crystals. Once these devices are operational at SwissFEL, the team will use them to investigate proteins of interest, particularly those currently untargetable by pharmaceutical compounds. The long-term vision includes adapting these devices for use at other synchrotron light sources globally, such as the Swiss Light Source SLS and DESY's PETRA III, to further advance the study of protein dynamics on an international scale.
Beyond the Headlines
The shift from laser pulses to electric fields for triggering protein dynamics represents a fundamental change in how protein function is studied, moving closer to physiological conditions. This approach acknowledges that electric fields play a vital role in biological processes, such as nerve signal transmission and enzymatic reactions. By mimicking these natural stimuli, researchers hope to gain more accurate insights into protein behavior, potentially uncovering mechanisms that have been overlooked by light-based methods. This could lead to a paradigm shift in drug discovery, enabling the targeting of previously inaccessible proteins and opening new avenues for treating complex diseases. The collaborative nature of the grant, involving multiple institutions, also highlights the increasing importance of interdisciplinary and international cooperation in cutting-edge scientific research.
