"Can I meet you tomorrow instead?"
Joerg Bewersdorf is in a hurry, and not just the usual scientist's write-this-grant-application-so-I-can-hire-that-postdoc kind of hurry, or finish-this-paper-today-because-I-have-a-conference-tomorrow kind of hurry. Dr. Bewersdorf is in a new kind of space race: competing with other top research institutions to see the smallest structures within a living cell.
Dr. Bewersdorf looks like a college undergrad, but is in fact a 36-year-old research scientist who joined The Jackson Laboratory's Center for Molecular Biophysics (CMB) in 2005. He works with the Laboratory's 4Pi confocal laser scanning microscope, the only instrument of its kind in the Western Hemisphere. Using opposing lasers, the 4Pi is capable of imaging the contents of a cell nucleus in three dimensions, at the unprecedented resolution of 100 nanometers. (For comparison, the paper this article is printed on is at least 100,000 nanometers thick.)
Like NASA scientists watching new space telescope images appear on their computer screens, Dr. Bewersdorf and his colleagues were the first people on earth to see some awe-inspiring natural structures. Branch-like Purkinje cells from the cerebellum part of the brain covered with unexpected doorknob-shaped protuberances. Chromosomes caught in the act of reproducing themselves in the cell nucleus.
But 100 nanometers' resolution is not fine enough for Dr. Bewersdorf and the rest of the CMB team. They're now working on a new-generation instrument, code-named "Biplane" as a pun on the microscope's scanning action along two planes, not just two axes like the 4Pi. "The ultimate goal," he says, "is to image proteins." That's right: to look directly at molecules."
Born with an eye for science
Given that Dr. Bewersdorf grew up in Aalen, Germany—headquarters of world-famous Carl Zeiss Inc., and dozens of other optical imaging companies—and had an early interest in astrophysics, it's only natural he would now spend his days, and many of his nights, working with high-resolution optical instruments. However, he says, "As a kid I was interested in cosmology and theoretical physics, not stargazing, and definitely not optics. And the funny thing is, I also thought biology was really boring. My dad was a medical doctor, and I had no interest in following in his footsteps."
Instead, Dr. Bewersdorf enrolled at the prestigious University of Freiburg to study physics. "But," he says, "it dawned on me that very few individuals are able to make a major impact on the field of theoretical physics. A typical project involves one giant particle accelerator and thousands of people—on a given day it doesn't really matter whether or not you show up for work!"
During a year as an exchange student at the University of Glasgow in Scotland, he gained a clearer picture of his career path. "I attended a lecture about medical physics, and then and there I decided to switch my studies to medical imaging," he says.
"I realized that I wanted to do work that mattered to people beyond a small group of colleagues and that helped people by advancing medical research." Thus returning from Scotland with a new mission, Dr. Bewersdorf moved to Heidelberg, a world center of applied physics in the medical imaging field. Wrapping up his undergraduate studies with a summer course in optics, he attended a lecture by Dr. Stefan Hell of the Max Planck Institute, an internationally prominent inventor of microscope technologies. Fascinated by Dr. Hell's work, Dr. Bewersdorf applied for an internship in his lab. He spent the next eight years there, completing the German equivalent of a Ph.D. (Dr. rer. nat.) and postdoctoral fellowship while also working at the Leica company developing one of Dr. Hell's inventions: the 4Pi microscope.
And so to Maine
Once the 4Pi technology was perfected, the first microscope to leave Heidelberg was destined for The Jackson Laboratory. The Laboratory had secured more than $1.2 million in funding from the National Science Foundation and the Keck Foundation to purchase the microscope and cover other expenses associated with operating it, including salaries.
"When I learned the Laboratory was hiring someone to work with the 4Pi, I knew I wanted to be that person," Dr. Bewersdorf says. "It was clear to me that the U.S. is truly the land of scientific opportunity, where so many German scientists had established successful careers.
"It was also time for me to leave Dr. Hell's lab," he comments. "In many ways that was the perfect work environment—all the funding you needed, the best applied optical physics lab in Germany—but I felt I had to prove I could work independently and make it on my own."
While Dr. Bewersdorf was building his career, his family was also growing, and he arrived in Bar Harbor with his wife Connie, then seven months pregnant with a daughter, Emmy, and 2-year-old daughter, Annika. "Naturally, Connie was a little apprehensive, moving to a foreign country with little ones," Dr. Bewersdorf says. "But she was also very excited and very supportive of my career. And just four weeks after we moved here some people we hardly knew had arranged a baby shower for Connie. That made us all feel very welcome and really helped to connect us quickly to the community." In December 2007, the Bewersdorfs welcomed a new baby, Philip, and all three of their children are thriving in their adopted country. Annika, now 5, plays in English, and 2-year-old Emmy is already bilingual.
Soon after joining the Center for Molecular Biophysics, Dr. Bewersdorf was struck by the collegial, even familial, atmosphere of The Jackson Laboratory. Welcomed by Center directors Dr. Barbara Knowles, vice president of the Laboratory for education, training, and external scientific collaborations, and Dr. Michael Grunze of the University of Maine and University of Heidelberg, he says he felt "they wanted to help me more than themselves. That's a great situation for a young scientist."
He also noted that the Max Planck Institute is almost as big as The Jackson Laboratory, but had only eight principal investigators, compared to 38 here. "At MPI the heads of each lab have too much to do just managing all the staff, and they don't really talk to each other," he says. "Our model is much more collaborative, which I think is better for science."
Teaming up for progress
In that spirit of collaboration, a number of Jackson Laboratory scientists in different fields have brought scientific questions to Dr. Bewersdorf that can only be answered by extremely high-resolution imaging.
For example, Jackson Assistant Professor Kevin Mills is studying defects in chromosomes that can lead to certain kinds of cancers, including childhood leukemias. "What is it about those chromosomes—how they're arranged, or how they're structured—that turns normal cells into abnormal ones?" Dr. Mills asks. "Scientists have been trying to get a good look at chromosomes for a hundred years, and only here and now, thanks to Joerg's team and the 4Pi, can we get this level of detail, almost down to the level of DNA fiber."
Seeing chromosomes that close up is more than just gee-whiz cool. Dr. Mills says it is the first step toward future cancer diagnostics. "The changes we're capturing on the 4Pi are occurring long before cancer actually begins. In a clinical setting, this opens the possibility of someday screening people for these subtle changes and designing strategies to prevent the cancer from occurring."
Today, with research assistants Mark Lessard and Michael Mlodzianoski, and undergraduate students Manuel Juette and Stefanie Kirschbaum of the University of Heidelberg, Dr. Bewersdorf is hard at work perfecting the next generation of nanoscale microscopes.
Microscopes are, in a sense, time machines. The smallest components of a living cell are also the fastest-moving, so there's a time dimension to consider in capturing images of them. "The single protein level, that's on the millisecond level," Dr. Bewersdorf notes. "To be able to observe structures on an individual protein—that's the goal."
Besides the excitement of invention itself, he says he's driven by "very strong, friendly competition" with some of the world's leading research institutions. The January edition of the influential journal Nature Methods cites "seeing fluorescence at super-resolution"—the technology behind the 4Pi and Biplane microscopes—as one of the top methods "on the cusp of profoundly impacting their field."
Dr. Bewersdorf believes that collaboration with colleagues at The Jackson Laboratory and partner institutions, including the University of Maine and University of Heidelberg, gives his team the edge in the race to inner space. "I want us to get there first," he says with quiet confidence.