SNSF Grant to push further the observations of protein dynamics

Proteins are the machinery of life and therefore inherently dynamic systems. Yet, much of what is known about proteins still derives from static structures, leaving the understanding of their function fundamentally incomplete. Observing proteins in action requires not only atomic spatial resolution, but also a temporal resolution that matches their fast motions — a challenge largely beyond the reach of existing methods in structural biology.

In recent years, the Laboratory of Molecular Nanodynamics, led by Ulrich Lorenz, has established a novel approach to cryo-electron microscopy (cryoEM) that enables atomic-resolution observations of protein dynamics with microsecond time resolution. This is notably fast enough to capture the large-amplitude domain motions of proteins typically associated with their function and thus promises to fundamentally advance the understanding of proteins. However, significant efforts remain to take this technique beyond the proof-of-principle stage and to develop microsecond time-resolved cryo-EM into a mature technique that can be broadly adopted.

The Consolidator Grant, a financial support from the Swiss National Science Foundation (SNSF), will help them push the boundaries further. “Several technical challenges will be overcome that currently limit the scope of the method. Specifically, its observation window will be extended to longer timescales and a variant will be implemented that affords nanosecond time resolution”, tells Ulrich Lorenz. To facilitate the adoption by other labs, a simpler implementation will be developed that does not rely on highly specialized equipment. The researchers are convinced that microsecond time-resolved cryo-EM can elucidate a broad range of previously inaccessible protein dynamics.