For a young scientist, Hari Shroff, co-director of the Optical Microscopy and Imaging course at MBL, has seen his share of career peaks. Shroff entered the University of Washington at age 14 and graduated when many people are just starting college. After completing his doctorate in biophysics in 2006 at the University of California, Berkeley, Shroff took the MBL Physiology course. It had “a huge influence on me,” Shroff says in this interview with Prashant Prabhat of Semrock. “I was working hand-in-hand with a lot of the experts in cell biology,” Shroff recalls, and they drove home how fundamental microscopy is to their field.

That same year, Shroff heard microscope developer Eric Betzig give a talk at Berkeley. “I have always been very fascinated by the fundamental mismatch in size between what a biologist wants to see and what they actually can see,” Shroff tells Prabhat. “[Betzig] was talking a little bit about super-resolution, and I wanted to drop what I was doing and immediately work for him.” Shroff felt lucky to become one of Betzig’s first hires at his lab at Howard Hughes Medical Institute’s newly opened Janelia Research Campus.

Shroff came back to the MBL Physiology course in 2007 as a teaching assistant, along with Betzig as visiting faculty. And there was important cargo in their van when they drove to Woods Hole: the super-resolution microscope Betzig and colleagues had invented, called PALM (photoactivated localization microscopy), which Shroff had a hand in developing. The scope’s power to visualize individual molecules at nanometer resolution bowled over the Physiology course participants and soon became the talk of the MBL campus.

“Those were very heady, exciting times, but also sleepless times,” Shroff tells Prabhat. “Something very special happens [at the MBL] during the summer when you have these world-class scientists congregating for a couple of months. You end up with these collisions which are just difficult to have otherwise. People have this kind of ‘can do’ attitude about science, and it’s also a great place for microscopy because some of the world’s best microscopists usually hang out there during the summers.”

Hari Shroff of the NIH shows MBL Neurobiology course students the light-sheet microscope he built (diSPIM). Credit: Tom Kleindinst

Hari Shroff of the NIH shows MBL students the light-sheet microscope he built (diSPIM). Credit: Tom Kleindinst

Important applications of Betzig’s microscope came out of that Physiology course session, which was led by course co-director Jennifer Lippincott-Schwartz of the NIH, an early collaborator with Betzig on PALM. These included live-cell, single particle tracking (sptPALM), which Betzig says “has become one of the most useful and biologically informative applications of the technology. That idea was born while we were waiting for a ferry ride in Woods Hole.” They also figured out how to label two colors of photo-activatable probes (double-color PALM) during the course, which Shroff et al published later that year.

In 2014, Betzig won a Nobel Prize in Chemistry for his contributions to super-resolution fluorescence microscopy. Shroff, meanwhile, had become a section chief at the NIH’s National Institute of Biomedical Imaging and Engineering. He was also invited to co-direct the Optical Microscopy and Imaging course, where he shows students how to build a microscope from scratch, among other challenges. The course is a lot of work, Shroff says, but “definitely fun. I actually get some of my best ideas just from daydreaming and talking to students.”