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Nikolaus Grigorieff
Like a photographer with a tightly focused lens, Nikolaus Grigorieff has spent the past decade visualizing tiny 3-D protein structures inside cells. Now he's ready to take a step back and survey a broader vista: the brain regions surrounding these structures.
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Nikolaus Grigorieff
HHMI Investigator
Brandeis University
Waltham, MA
Photo: ©Paul Fetters
A high-resolution photograph is available on request.
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Grigorieff uses high-resolution electron microscopy and develops new methods of image processing to reveal the structures of proteins and protein complexes. Although he primarily studies protein complexes isolated from cells, some of the structures beneath his microscope—such as membrane proteins that trigger neural communication—play pivotal roles in the brain. "I've been focused on single components, but I'm increasingly interested in the whole system," Grigorieff says.
In particular, he'd like to visualize what happens at the synapse: the point of communication between two neurons. "To many scientists, synapse terminals are just a block of dense material, and it's unclear how they are built and how they respond to changes in stimuli," Grigorieff says. "That's probably something we can study with electron microscopy." He'd like to develop high-resolution techniques to section, or thinly slice, a synapse at different stages of action.
"At Janelia Farm, I hope to collaborate with neurobiologists and learn more about the brain," Grigorieff says. "I'm coming to learn about a new field." And Janelia Farm is a unique environment for this, he adds: "With just six lab members in each group, we will be pushed to collaborate more than at traditional academic institutions."
At Brandeis University, where he is an HHMI investigator, Grigorieff and colleagues already have used single-particle electron microscopy to capture the 3-D structure of key components in a membrane protein known as the Shaker potassium channel—a voltage-gated ion channel that triggers communication between neurons. Similarly, Grigorieff's lab helped unravel critical structures in another potassium channel, dubbed Kv4.2, as well as structures in chloride ion channels.
When Grigorieff arrives at Janelia Farm, he will bring along a separate long-term project, determining the 3-D structure of the spliceosome—a complex of protein–RNA machinery inside cells that splices together the blueprints for proteins. Although this effort (a collaboration with HHMI investigator Melissa Moore at Brandeis) is not directly related to neurobiology, the techniques may prove useful across fields. Grigorieff is developing image processing methods to extract small, high-resolution details of the "molecular machine," as he calls it.
In some ways, his move toward neuroscience reflects an ongoing intellectual journey. Initially trained in physics as a materials scientist, Grigorieff gravitated toward biophysics as a postdoctoral research fellow studying protein structure at the MRC Laboratory of Molecular Biology in Cambridge about a decade ago.
Looking ahead to his time at Janelia Farm, Grigorieff anticipates breaking free from the constraints of conventional research. "At Janelia Farm, the emphasis is on trying to discover fundamental principles that cannot emerge from a proven, routine mechanism. It's quite different." As his research path reflects, Grigorieff embraces the different.
Nikolaus Grigorieff received a First-Grade degree in physics from the Technical University in Berlin and an M.Sc. and Ph.D. in physics from the University of Bristol. He is an HHMI investigator and Associate Professor of Biochemistry at Brandeis University. He has received a Humboldt Foundation research fellowship and the New Investigator Award from the Medical Foundation of Boston.
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