The sun floods into the Physiology course break room at the Marine Biological Laboratory (MBL) less than a block away from the narrow inlet between the mainland and Naushon Island that gives Woods Hole, MA, its name. Woods Hole is at the shoulder of Cape Cod, a popular summer vacation destination. In the harbor, vintage sailboats carry sunbathers, giant ferries take tourists to Martha's Vineyard, and the MBL work boat brings squid harvested from Vineyard Sound to neuroscience labs. But the 27 graduate students and postdocs who are enrolled in MBL's legendary Physiology course have little time for the sights. Instead, the students use the break room to refuel, analyze data, and argue about PALM vs. STORM or the latest on tropomyosin. Then it's back to the Physiology lab where the students live 16 hours a day for seven weeks. Asked about a famous beach up the road, a Physiology student sighed, "I've been there once."
"Break room" is a bit of a misnomer. The countertops are littered with quick rations and fortifiers—trail mix, Skippy peanut butter, a pair of coffee makers, Folgers cans, an empty case of Sierra Nevada Pale Ale, and a family size container of Chips Ahoy. The white board features scrawled multicolored formulas for yeast bud initiation and mean curvature, as well as a drawing of a guy with a Mohawk. In the background, Bob Marley sings to students focused on screens cluttered with the morning's data. The pace is grueling and yet most of the Physiology students love the experience. Woods Hole in summer is that kind of place.
MBL started as a research station in 1888 and since then 55 Nobel laureates have been affiliated with the institution. This summer, five Nobelists were there conducting research, including Avram Hershko, who won the Nobel Prize in 2004 for the discovery of ubiquitin-mediated protein degradation. Graduate students and postdocs come from around the world to learn in 22 intensive courses including embryology, neuroscience, and physiology. The Physiology course was started at MBL in 1892 by the German-born biologist Jacques Loeb, who was renowned for his demonstration that sea urchin eggs could be induced to develop into embryos without sperm. It was the second course started at MBL, just after the Zoology course.
Most students come because they catch the buzz from former students about the opportunities Physiology offers—the chance to rub shoulders with research giants, the energetic environment, and the long-term friendships and collaborations that result. Admission is competitive and students who get in generally have part of their tuition covered in part by their home institution. Various fellowships, grants, and private donations cover much of the rest including room and board in MBL dorms. The course is intense but distractions are minimized, says Ron Vale, of the University of California, San Francisco (UCSF), who discovered kinesin as a graduate student at MBL and is both a former Physiology course director and a former ASCB president. "Back at the universities, students have a lot of other things to do, like thesis writing." Vale says that being away from everyday life—cooking, commuting, TA-ing, or thesis writing—gives students time to focus on the work.
Physiology kicks off with a one-week "boot-camp" in which students learn biochemistry, microscopy, image analysis, and the programming software, MAT-LAB. "The boot camp sets the tone for the course. Computational scientists are helping the biologists with MAT-LAB and biologists are helping physicists with a protein prep. They start helping one another with things that they're good at," said Vale over the hum of a vortexer.
After boot camp, the students spend two intensive weeks in three different areas of research. During each rotation, students work in small groups with assigned faculty leaders to conduct experiments and analyze data to address scientific questions that instructors bring to the course. "We [instructors] try to bring questions that we struggle over as much as the students do... so we can struggle together" said Dyche Mullins, one of two course directors and a UCSF professor. The process produces results. Physiology students published 23 research papers and presented 59 meeting abstracts between 2005 and 20121.
This summer at least four students will be presenting their work from MBL at the ASCB Annual Meeting. Einat Schnur, postdoc at the London Research Institute, Ernest Heimsath, postdoc at the NIH, Batbileg Bor, graduate student at the University of California, Los Angeles, and Sofia Espinoza Sanchez, graduate student at Yale, worked together on a cell motility project with guidance from course instructor Jennifer Lippincott-Schwartz, who is the ASCB President-Elect, an intramural investigator at the NIH, and an expert on emerging "big data" imaging technologies. Their work was based on the observation that when sea urchin eggs are torn open, the cytoplasm does not disperse, but gets sucked back in. "What are the underlying proteins and mechanisms involved in that process?" Heimsath and his lab partners wanted to know. They looked at mammalian COS-7 cells that expressed tagged annexinA2, a calcium-dependent membrane binding protein. It took only 13 days for the group to generate data and a first draft.
A day for the Physiology students begins at 8:30 am with breakfast in the MBL cafeteria, across from the dorms and labs. Physiology students usually sit together, often joined by course instructors and course directors. After breakfast, course instructors and prominent scientists give talks. By lecture's end, students are ready to get to the lab. They work until around noon before trooping back to the cafeteria, where lab talk doesn't stop. Then more experiments until dinner, and more lab work after that.
Every day at 5:00 pm, students take turns giving a 30 minute "chalk talk" with white board markers. Why no PowerPoint? "You have to be able to do a chalk talk because in the middle of any scientific discussion you have to be able to go to the board and explain what you are talking about. You don't always have PowerPoint to lean on," Mullins explained.
Several times each week lab groups working in similar research areas meet together to discuss results. During these meetings, course directors and instructors challenged students to think critically about their experiments. "Are you using the right technique to answer the question?" asked Clare Waterman, who is the other Physiology course director and an NIH intramural researcher.
Rooms in the center of the Loeb lab building are equipped with advanced, high-resolution microscopes. The instruments are booked in three-hour shifts 24 hours a day, and a look at the sign-up sheet revealed that there were bookings even for the 3:00 am-6:00 am slot.
On Sundays, students catch up on sleep.
The intensity creates lasting friendships and scientific collaborations. Hari Shroff, who is now an instructor, was a Physiology student in 2006. Shroff and three of his Physiology friends ended up taking a six-week roadtrip across Europe in 2009. They still stay in touch. Course directors Mullins and Waterman first worked together while Physiology students in 1993 and now collaborate during the summer.
For what they gain at MBL, one thing Physiology students leave behind is fear. "I lost the fear of feeling stupid," one student said. Other students say they lost their fear of exploring new directions in research or even of ditching a project that's not progressing. "Here there's not much at stake, people are exploring, having fun, learning new things," says Vale. "I think that over time we learn to not be afraid of asking dumb questions."
"I try to get everyone to take the Physiology course," said Rob Phillips, Physiology course instructor and professor at California Institute of Technology. "They come home as different people. One of the things they leave with is a fearlessness that they didn't have. I think that that's very important in science to play around and try stuff... then you're more inclined when you go home to try things."
Despite the long hours, the students do have a unique MBL kind of fun in the lab, as witnessed by last year's high-speed filming. This year, squirt guns were scattered around lab benches and break areas. In the corner of the break room there was a stack of foam pool noodles. Students disagreed on the purpose of the noodles. One student said they were to keep speakers to time during seminars, whacking those who run over. Another explained they kept time just by being held aloft. A third person said the noodles were cilia used in cellular reenactments.
To celebrate the end of the course, students and instructors took an MBL research vessel to a private beach in the nearby Elizabeth Islands for a lobster feast. On the voyage out, the Physiology students lined the rail. After a summer deep in the microscopic world, they finally had a chance to see the macroscopic beauty of Woods Hole.