A Schmidt Grant and a Bold Idea for Imaging

When Martin Jonikas gave his flash talk at a Princeton Catalysis Initiative Symposium in 2019, he tucked a couple of hopeful words at the bottom of a presentation slide to invite faculty partners for his research on CO₂ uptake in plants.

One of those words caught the eye of a specialist from the Rabitz Lab at the Department of Chemistry who was sitting in the audience.

Jonikas, an associate professor of Molecular Biology, hoped to capture the minute interior landscape of plant cells with imaging technology that did not—and still does not—exist. The specialist, Alexei Goun, saw the word “imaging” in the presentation and thought: Yep. We can help with that.

Many conversations and three years later, their collaboration has fully launched, bolstered last week by an Eric and Wendy Schmidt Transformative Technology Fund award. It may well result in the first technology able to map small molecules in their living environments on a resolution close to the atomic scale.

Right now there is no instrument capable of doing that. The achievement would be transformational for biologists like Jonikas and anyone else who might need high-resolution imaging in areas from medicine to the geosciences.

Titled, “Breaking through the spatial resolution and chemical selectivity barriers in biological chemical imaging,” the project is one of just three to receive a Schmidt award this year. The Fund celebrates bold new ideas that can accelerate progress in science and engineering, pioneer new discoveries, and transform entire fields of inquiry.

The award pairs the Jonikas Lab with the lab of Herschel Rabitz, Charles Phelps Smyth ’16 *17 Professor of Chemistry.

“We’re going to attempt to create a multi-step imaging system by combining advanced tools from nano-science, optical science, and complex data analytics that will reveal internal cell structure at the molecular scale,” said Rabitz.

“Right now—and people are always surprised to hear this—the ability to see at the molecular scale is very limited. We’ll be using lasers in a novel way that’s not been done before. There are risks here, but we’re at the threshold. If it all works out, it’ll be fantastic.”

Of the difficulty inherent in the project, Goun added simply: “It takes a lot of technology to see very small things.”

Ultra-High Resolution Imaging

The team will combine ultra-high-resolution imaging with ultra-high sensitivity in the detection of biological molecules, investigating one of the most important molecules to society: carbon dioxide. They’ll focus on how plant cells can commandeer carbon dioxide and remove it from the atmosphere.

Researchers will put the system to the test once Jonikas trains it on plant cells to reveal the concentration of CO₂ at very specific locations within the cells. This goal has been a technical challenge in his work for over a decade now. Several attempts to access these locales through other means—for example, protein sensors that bind to small molecules—have not been successful.

“Photosynthetic organisms drive the global carbon cycle by taking up CO₂ from their environment,” said Jonikas, who is also a Howard Hughes Medical Institute Investigator. “Many of these organisms have mechanisms to enhance this uptake, but little is known about how they work. To understand these mechanisms, we need to see where the CO₂ is going within the cell.

“The capabilities of the planned instrument enabled by the Schmidt award will allow us to see where the CO₂ is going within the cell and will help us understand the mechanisms that enhance its uptake. This biological problem will serve as an ideal proof-of-concept for the technology.”

Researchers wrote the Schmidt proposal so that it focuses on CO₂, which has certain unusual spectroscopic characteristics that make it fairly easy to isolate. They anticipate the device will eventually employ a voxel—the 3D equivalent of a pixel—moving over the plant cell to take thousands of tiny images.

The whole cell will then be a concatenation of these images, each one telling a different story about what’s in that part of the cell, chemically.

“The sensitivity will be at the level where we’ll hopefully be able to tell, it’s this biological molecule and not that one, and so on,” said Rabitz. “What Martin wants to do is essentially a biology project, but he can’t do that without this instrument. It would be transformative. And so here the three of us are. It’s a perfect, classic relationship.”

The Eric and Wendy Schmidt Transformative Technology Fund was created through support from Eric Schmidt, the former chief executive officer of Google and former executive chairman of Alphabet Inc., Google’s parent company, and his wife Wendy Schmidt. The Schmidts created the $25 million endowment fund for the invention, development, and utilization of cutting-edge technology that has the capacity to transform research in the natural sciences and engineering. Schmidt earned his bachelor’s degree in electrical engineering from Princeton in 1976.