By Jim McIlvain

A group of MBL researchers gathered recently to celebrate the birthday of Ernst Abbe (1840 – 1905), the physicist credited with discovering the resolution limit of the light microscope. Abbe-birthday-cake-webAbbe published the formula (known as Abbe’s diffraction limit, and inscribed here on the birthday cake) in 1873, while he was research director at Zeiss Optical Works in Jena, Germany. This new understanding of optical theory, along with many of his other inventions, heralded the modern era of microscopy.

Today, the MBL continues its long tradition of exploration at the forefront of microscopy. Ongoing research seeks to circumvent Abbe’s resolution limit by a combination of optical and computational manipulation in image space. In 2014, the Nobel Prize in Chemistry recognized “super-resolution” imaging technologies that get around Abbe’s resolution limit.

MBL researchers celebrating Abbe’s birthday are, from left, Jim McIlvain, Carl Zeiss Microscopy senior application specialist at MBL; Jessica Mark Welch, associate research scientist; Rudolf Oldenbourg, senior scientist; Kasa Hammar, microscopy technician (seated); Shane Jinson, research assistant; Eric Edsinger, research fellow; Louie Kerr, director, Microscopy & Research Services. Behind the camera: Shalin Mehta, postdoctoral fellow.

Celebrating Abbe’s birthday are, from left, Jim McIlvain, Carl Zeiss Microscopy senior application specialist at MBL; Jessica Mark Welch, associate research scientist; Kasa Hammar, microscopy technician (seated); Rudolf Oldenbourg, senior scientist; Shane Jinson, research assistant; Eric Edsinger, research fellow; Louie Kerr, director, Microscopy & Research Services. Behind the camera: Shalin Mehta, assistant research scientist.


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.”


If you check the MBL’s Twitter feed during the summer months, you’ll be treated to quick, highly enthusiastic, and often visually beautiful dispatches from the MBL’s Summer Courses. The students and faculty are pursuing up-to-the-minute questions in life sciences research using a wide array of high-end imaging equipment, and some of the images they produce are eye-popping. Here are just a few recent Twitter posts from MBL students and faculty:

Vincent Boudreau (@viboud), a graduate student in the Physiology Course from University of North Carolina, Chapel Hill, Tweeted out this video, which he and several students made during the course’s biochemistry bootcamp under the supervision of Sabine Petry of Princeton University and Robert Fischer of the National Institutes of Health. “This bootcamp experiment taught us students how to do the biochemical legwork involved to get these microtubules to give us such stunning images,” Boudreau says. Microtubules (red) can be seen branching off of one another, marked by the green EB1 protein at their outwardly growing extremity. Video made with a Nikon TIRF microscope.

The MBL Embryology Course, tweeting under the hashtag #embryo2015, has shared one striking image after another. This is a tardigrade (a bizarre-looking, microscopic, water-dwelling animal) imaged with light-sheet microscopy by two students in the course: Christina Zakas, a post-doc at New York University who tweets @CZakDerv, and Nick Shikuma, a post-doc at Caltech.


Tardigrade stained with DAPI to highlight nuclei and imaged on the Zeiss lighsheet Z1. Credit: C. Zakas and N. Shikuma, MBL Embryology course

Speaking of Embryology, several students in the course are blogging about their MBL experiences at the Node, an online community resource run by The Company of Biologists.  Check out their impressions of the course — its sheer intensity, its “exquisite coordination,” and the fun that balances all the hard work.

Embryology Course Co-director Alejandro Sánchez Alvarado, an expert Tweeter, once in a while reminds the students to step back from the bench, take a deep breath, and enjoy the beauty of Woods Hole. He called this scene “the rewards of Eel Pond after a rich day of learning and experimentation.”

Eel Pond, Woods Hole. Credit: Alejandro Sánchez Alvarado of the Stowers Institute/HHMI

Eel Pond, Woods Hole. Credit: Alejandro Sánchez Alvarado of the Stowers Institute/HHMI


The Oosight(R) product line of microscopes, developed at the MBL  and commercialized by Cambridge Research & Instrumentation, Inc. (CRi), has been acquired by Hamilton Thorne, Ltd., a provider of precision laser devices and image analysis systems for the fertility, stem cell, and developmental biology research markets.

Widely used in fertility clinics to assess the health of unfertilized eggs (oocytes), the Oosight system provides live, high-contrast images and captures quantitative data on important oocyte structures using a patented, non-invasive, polarized-light technique. The technology was developed at the MBL by Rudolf Oldenbourg, Michael Shribak and colleagues in the 1990s and 2000s and commercialized by CRi as LC-PolScope(TM) technology. The Oosight system’s visualization capabilities have enabled breakthroughs in assisted reproductive technology, stem cell generation, and developmental biology research.

Visualization of the meiotic spindle in a rhesus monkey oocyte (egg) using the OosightTM spindle imaging system during enucleation. The spindle is near the 12 o'clock position in the egg. Credit: From Byrne, et al. 2007. Nature 450: 497-502 (Supplementary Material).

Visualization of the meiotic spindle in a rhesus monkey egg using the Oosight spindle imaging system during enucleation. The spindle is near the 12 o’clock position in the egg. Credit: Byrne et al (2007) Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature 450: 497-502.

“The Oosight system is a unique instrument that is complementary to our laser products in both fertility and developmental biology research labs,” remarked David Wolf, President and CEO of Hamilton Thorne. “As a long-term distributor of the Oosight system we have already completed the technical integration of the Oosight with our laser products. We believe that by leveraging our established, world-wide sales channels and investing in product marketing, we can generate incremental sales of the Oosight product.”

Additional information on the Oosight product and its multiple applications can be found at


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Contact: Diana Kenney, Marine Biological Laboratory

WOODS HOLE, Mass.—How a brilliant-green sea slug manages to live for months at a time “feeding” on sunlight, like a plant, is clarified in a recent study published in The Biological Bulletin.

The authors present the first direct evidence that the emerald green sea slug’s chromosomes have some genes that come from the algae it eats.

These genes help sustain photosynthetic processes inside the slug that provide it with all the food it needs.

Importantly, this is one of the only known examples of functional gene transfer from one multicellular species to another, which is the goal of gene therapy to correct genetically based diseases in humans.

“Is a sea slug a good [biological model] for a human therapy? Probably not. But figuring out the mechanism of this naturally occurring gene transfer could be extremely instructive for future medical applications,” says study co-author Sidney K. Pierce, an emeritus professor at University of South Florida and at University of Maryland, College Park.

The rich green color of the photosynthesizing sea slug, Elysia chlorotica, helps to camouflage it on the ocean floor. Credit: Patrick Krug

The rich green color of the photosynthesizing sea slug, Elysia chlorotica, helps to camouflage it on the ocean floor. Credit: Patrick Krug

The team used an advanced imaging technique to confirm that a gene from the alga V. litorea is present on the E. chlorotica slug’s chromosome. This gene makes an enzyme that is critical to the function of photosynthetic “machines” called chloroplasts, which are typically found in plants and algae.

It has been known since the 1970s that E. chloritica “steals” chloroplasts from V. litorea (called “kleptoplasty”) and embeds them into its own digestive cells. Once inside the slug cells, the chloroplasts continue to photosynthesize for up to nine months—much longer than they would perform in the alga. The photosynthesis process produces carbohydrates and lipids, which nourish the slug.

How the slug manages to maintain these photosynthesizing organelles for so long has been the topic of intensive study and a good deal of controversy. “This paper confirms that one of several algal genes needed to repair damage to chloroplasts, and keep them functioning, is present on the slug chromosome,” Pierce says. “The gene is incorporated into the slug chromosome and transmitted to the next generation of slugs.” While the next generation must take up chloroplasts anew from algae, the genes to maintain the chloroplasts are already present in the slug genome, Pierce says.

“There is no way on earth that genes from an alga should work inside an animal cell,” Pierce says. “And yet here, they do. They allow the animal to rely on sunshine for its nutrition. So if something happens to their food source, they have a way of not starving to death until they find more algae to eat.”

This biological adaptation is also a mechanism of rapid evolution, Pierce says. “When a successful transfer of genes between species occurs, evolution can basically happen from one generation to the next,” he notes, rather than over an evolutionary time scale of thousands of years.


Schwartz JA, Curtis NE, and Pierce SK (2014) FISH labeling reveals a horizontally transferred algal (Vaucheria litorea) nuclear gene on a sea slug (Elysia chlorotica) chromosome. Biol. Bull. 227: 300-312.


The Biological Bulletin is a peer-reviewed, trans-disciplinary international journal that publishes outstanding experimental research on a wide range of organisms and biological topics, with a focus on marine models. Published since 1897 by the Marine Biological Laboratory, it is one of America’s oldest and most respected journals.

The Marine Biological Laboratory (MBL) is dedicated to scientific discovery and improving the human condition through research and education in biology, biomedicine, and environmental science. Founded in Woods Hole, Massachusetts, in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago.

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