Development of Stroboscopic Cryo-electron Tomography

Cryo-electron tomography (cryo-ET) has the potential to revolutionize our understanding of biology, delivering high-resolution structure determination to unique objects in situ inside frozen-hydrated cells. Currently, this potential is limited by two factors: low throughput and poor image quality. Tens to hundreds of thousands of particles are needed to calculate a near-atomic-resolution subtomogram average of a protein complex; collecting this amount of data is currently prohibitive for anything but a few ideal cases. In addition, tilted images are almost always of worse quality than untilted images of the same object, likely due to drumhead-like trembling motion of the sample normal to the grid.

Grant Jensen will embark on a high-risk, high-reward project to test three approaches in order to develop a method for “stroboscopic cryo-ET” that will remove these limitations and allow researchers to collect high-quality tilt-series in seconds and resolve the near-atomic-resolution details of many protein complexes in their native state inside cells. This first phase aims to provide proof of principle for the method. If successful, Jensen will then pursue a second phase to demonstrate its applicability to biological targets.