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Neuronal Cell Biology Comes to Janelia

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Neuronal Cell Biology Comes to Janelia

The Neuronal Cell Biology Program will support scientists investigating the structural and functional details of discrete neurons and exploring the inner landscape of these cells.
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Neuronal Cell Biology Comes to Janelia
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03/15/16 | Neuronal Cell Biology at Janelia

After nearly a decade of advancing circuit-level neurobiology and imaging, Howard Hughes Medical Institute’s Janelia Research Campus is expanding its scientific horizons to encompass the cellular realm. Highlighting the new initiative is the launch of a Neuronal Cell Biology Program that will support scientists investigating the structural and functional details of discrete neurons and exploring the inner landscape of these cells in dynamic neural environments.

As the new program gears up, it will foster a fertile ground for a handful of incoming scientists, including Jennifer Lippincott-Schwartz, who is moving to Janelia after 23 years as chief of the section on organelle biology in the Cell Biology and Metabolism Program, in the Division of Intramural Research at the National Institutes of Health (NIH). Among the questions on her list: How do organelles migrate within a neuron to propagate a synapse? What happens to the function of a nerve cell if other chemicals, like nicotine, are introduced? How do specific proteins migrate throughout the neuron to accomplish a task? These are the kinds of inquiries that innately interest her, Lippincott-Schwartz says, and that she believes can provide a framework for study of larger neuronal systems in the brain.

What is Neuronal Cell Biology?

The inner workings of neurons – as compared to other cell types – remain largely ambiguous. Neurons are responsible for sending and receiving a wide range of information involved in everything from sensing a hot stove to learning a new language, and to do so, they transmit signals within networks called circuits. Neuronal cell biology is a deep-dive into the individual unit of the circuit, the neuron. Learn More

To establish the program, Lippincott-Schwartz will be joined by Janelia Group Leader James Liu and Senior Fellow Rob Singer, as well as Kelsey Martin, a neuronal cell biologist at the University of California, Los Angeles, who has recently become a Janelia Senior Fellow.

Gerald Rubin, HHMI vice president and executive director of the Janelia Research Campus, agrees that understanding the inner operations of a neuron is crucial to comprehending neural circuitry as a whole. What’s more, he notes, many of the imaging tools at Janelia are best suited for single-neuron analyses, rather than circuitry. Through adapting these tools, Rubin envisions the Neuronal Cell Biology Program as a means to bridge Janelia’s existing research areas.

“The way to have maximum impact is by doing important things that other people aren’t doing,” says Rubin. “[Neuronal cell biology] is a key area that we believe is currently underappreciated relative to its importance in understanding how the brain works, and our particular expertise makes us very well suited to make a contribution to it.”

Rubin is optimistic that the new program will catalyze growth in neuronal cell biology. “We try to shift into areas where we have unique capabilities and we think that, because of our imaging instruments, patient mode of funding, and expertise in circuit neurobiology, we can do experiments [in neuronal cell biology] that wouldn’t be done elsewhere,” he says.

Though all the boxes have yet to be unpacked, Lippincott-Schwartz’s transition will likely be a smooth one – even before she anchored her lab at Janelia, she was no stranger to the sprawling, glass-walled campus. As a cell biologist at NIH, Lippincott-Schwartz maintained strong ties with colleagues Eric Betzig and Harald Hess, group leaders and microscopy experts at Janelia. Periodically, Lippincott-Schwartz would visit Janelia to test their latest microscopy advances and apply the cutting-edge developments to her own research projects. With the help of tools like the lattice light sheet and Bessel beam microscopes, Lippincott-Schwartz’s experimental results fluoresced in colorful, high resolution and Betzig and Hess were able to build on her biological expertise to improve their imaging systems. Now, that collaboration can continue from within Janelia.

“The only thing that matters is the scientific understanding that comes out of an instrument – if the tool just sits there and dies on the vine, it’s no good,” says Betzig. “It has to be disseminated to get feedback, and Jennifer has always been one of our go-to people when we have a new widget to try.”

Group Leaders in Neuronal Cell Biology

Another potential collaborator at Janelia, Group Leader Karel Svoboda, points out that the brain is made up of an enormous ensemble of neurons – mice have nearly 75 million, while humans have around 100 billion. Svoboda is interested in how these cells “talk to each other” to form highly complex neural circuits that govern animal behavior. “We want to know how neurons are hooked up together, and we want to measure what they are doing in the brain. But we also want to be able to manipulate individual cells, to see what that does to the whole system,” he says. “If we understood neuronal cell biology – what all the cells are doing and what other molecules are doing during specific synapse events – then we could harness that knowledge to intervene and read out the activity of synapses.”

Tools like the lattice light sheet microscope and the total internal reflection fluorescence microscope will be instrumental in this collaborative exploration, enabling scientists to analyze how organelles and proteins move inside the neuron to carry out specific functions, like propagating a circuit. “Janelia offers an incredible opportunity to move with developing technology that enables fundamental cell biology questions to be addressed. At the same time, there’s a rich bedrock of people here who are doing really spectacular neurobiology,” says Lippincott-Schwartz. “There’s a huge amount of cell biology that is unclear, as it relates to neurons. I'm not a born-and-bred neurobiologist, so it’ll be a real blast to interact with these scientists to figure out what’s driving the biology of the neuron.”

As the Neuronal Cell Biology Program ramps up, Rubin emphasizes that he and others at Janelia will continue to be on the lookout for exceptional, impassioned scientists. He notes that the success of this program will likely depend not only on neuronal cell biologists, but also on other specialists working in areas such as physics, image analysis, engineering, and chemistry as well as cell biologists who want to move their research into neurons. Their collective insights and expertise will help Janelia scientists create new ways to manipulate neurons, image them, and analyze the resulting data.