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Visualizing Proteins of the Nuclear Pore

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Martin Beck
Title: Postdoctoral Fellow, Institute of Molecular Systems Biology, ETH Zurich
Education: PhD, The Technical
University of Munich, 2006
Recommended by
: Ruedi Aebersold

Before even beginning his PhD, Martin Beck spent some time in Günter Blobel's lab at Rockefeller University. There, Beck was exposed to the field of nuclear-cytoplasmic transport, which he continues to study. Working in a Nobel laureate's lab at such an early and impressionable stage in his career inspired Beck to develop his scientific skills more systematically — so he pursued a PhD at the Max Planck Institute for Biochemistry.

At Max Planck, Beck continued working on the nuclear pore, but also expanded to take on structural biology. He then decided that mass spectrometry would be a good complementary tool for determining protein structure. As a postdoc with Ruedi Aebersold at the Institute of Molecular Systems Biology, Beck has been learning mass spec and developing technologies to combine it with electron microscopy.

Beck will soon be setting up his own lab at EMBL in Heidelberg, where he will be a group leader in the Structural and Computational Biology Unit. There, Beck will combine what he's studied at Rockefeller, Max Planck, and the Institute of Molecular Systems Biology. "I've decided basically biology-wise to go back to the field of nuclear pore complexes and apply approaches that I've been developing now during my postdoc, which is ... measuring protein quantities using mass spectrometry and getting three-dimensional [information] using 3D cryo EM," he says.

For both technologies, the challenge is sample complexity, Beck says. "If you acquire a tomogram of a living cell, it basically contains all the electron optical densities of all the molecules inside and the difficulty there is to assign who is who — to know which proteins correspond to the electron optical density," he says. "In terms of mass spectrometry, it's a similar problem, particularly if you work on human cells or eukaryotic cells. The amount of peptides that you have to cope with is really so enormous that it is getting difficult to measure such samples."

Looking ahead

While it is difficult to divine the future, Beck says he hopes that advances will be made in integrating data. For large macromolecular proteins, he says, X-ray crystallography and mass spec data, among other sources of information, say something about the protein. "The challenge ahead is to integrate all this information from different labs in a meaningful way into structural models from which we can actually learn something," he says.

Publications of note

Back in 2007, Beck was the first author on a Nature paper, "Snapshots of nuclear pore complexes in action captured by cryo-electron tomography," in which they used tomography to look at the nuclear pore complex over time. "The superposition of a large number of tomograms taken in the presence of cargo, which was rendered visible by gold nanoparticles, has yielded a map outlining the trajectories of import cargo," the authors write.

In Nature Methods this November, Beck and his colleagues published a paper entitled "Visual proteomics of the human pathogen Leptospira interrogans." Beck says, "Technology-wise, it's about combining EM and mass spectrometry." Specifically, he and his co-authors write that they "combined quantitative mass spectrometry and cryo-electron tomography to detect, count and localize specific protein complexes in the cytoplasm of the human pathogen Leptospira interrogans."

And the Nobel goes to.../strong>

Beck notes that most Nobel laureates win for work they "have actually done when then are much younger than I am now." Because of that he thinks his chances aren't that good, but if he were to win, "I wish I could win for something that would be a great benefit for mankind," he says.

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