Speaking to the assembled masses at the American Society for Cell Biology meeting last December, Wolfgang Baumeister presented an intriguing vision for the future of electron microscopy. What if, he asked, instead of capturing two-dimensional images of the inner workings of the cell — a format that compresses visual data into just one plane — one could create three-dimensional images of the cell’s entire proteome, while simultaneously identifying every protein in the image?
It would be nice.
And Baumeister thinks he can do it. Long a proponent of electron tomography, a technique that mathematically assembles 2-D datasets into one 3-D image, the structural biologist at the Max-Planck Institute for Biochemistry in Martinsreid has devised a plan for freezing samples, collecting 3-D images with electron tomography, and rapidly identifying every protein in the cell with the aid of previously generated images showing the proteins in a variety of orientations. High-resolution cryoelectron tomography, he says, “can essentially create 3-D images of the cell’s entire proteome, and depict the network of interactions that orchestrate higher cellular function.”
So far Baumeister has performed validation experiments just with “phantom cells” — that is, artificially created cells containing well-characterized complexes such as proteasomes — and there are challenges to working with the real thing. Electron tomography often produces data with a high signal-to-noise ratio, the cytoplasm is a relatively crowded environment, and the cell has a finite resistance to the radiation used to generate the image.
But Baumeister isn’t the only one optimistic that it just might work. “It’s a very exciting prospect,” says David Stokes, a structural biologist at New York University. “There are others doing cryoelectron tomography, but Wolfgang is the most ambitious.”
— John S. MacNeil