Course


By Niteace Whittington
Whittington, from Philadelphia, PA, is a Postdoctoral Fellow at the National Institutes of Health (NIH), and took the 2015 SPINES course.

“Why are you here?” It is a question a faculty member posed on my first day at the MBL. At the time I had no answer. I never thought too deeply about what I did in life. I did not know what my ultimate goals were and certainly did not know how to bring them to fruition. I simply did the things I liked to do, but I did not know my purpose. During my month at the MBL, I was forced to address this question head-on, and I now have an answer thanks to the Summer Program in Neuroscience, Ethics, and Survival (SPINES).

SPINES-NW-1SPINES is a four-week, intensive course held yearly at MBL. It focuses on enhancing under-represented minority students’ success in neuroscience through research, career development, mentoring and encouragement. I had previously attended programs with similar goals; so I assumed that I would learn about cool research, receive tips on career development, and part ways from the group as I had done before. I was not expecting to learn more about myself, make lifelong friends, and have concerned mentors to help map out my life goals. I really thought SPINES would be like any other course. I can honestly say that I am thrilled to find I was completely wrong!

It was one of the course’s co-directors, Jean King of University of Massachusetts Medical School, who asked us “Why are you here?” With this question she challenged us to explore and share our true selves, and assured us that we were not alone in our journeys. Hearing some of my classmates speak, I found that many of us were facing similar trials and some of us had lost our love for research. As I thought about my purpose a little longer, I had some ideas about what I wanted in life but realized I had no direction. Self-assessment revealed that I was not sure that I could actually get to where I wanted to go. According to several depressing statistics, I chose the wrong field for my race and gender: I have a lower likelihood of success because I am a black woman. For a while I let this dictate how far I could go in life.

However, my SPINES family made sure I would never think that way again. One of the most striking aspects of the course was that directors (King, Keith Trujillo of California State University San Marcos and Eddie Castañeda of University of Texas at El Paso) showed continuous love and support for our individual endeavors. They not only worked with us to build our knowledge in neuroscience, ethics, and career survival, but also helped build our confidence, discussed our goals and issues, and helped us develop methods to address these things in beneficial ways.

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Throughout the SPINES course, in the midst of coursework reading, lab work, lectures and seminars, we did a lot of self-reflection and addressed our strengths and weaknesses in order to better map out who we are, what we want in life, and how to get there. In the course of one month, SPINES showed me that with the right tools I can do anything I aspire to do, as long as I believe in myself and my capabilities. On the last day, we took time to visualize a goal or dream that we wanted to achieve. And for the first time, I actually saw myself running my own lab and performing award-winning research. SPINES gave me confidence to walk down this road that I envisioned as unpassable. So why am I here? I am here because I have a job to do. Thank you, SPINES!

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.

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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

 

By Kelsey Calhoun

Chronic pain gets a fair amount of attention from researchers, but chronic itch, such as eczema or psoriasis, can cause just as much distress. Chronic itch can result from a variety of skin, nervous system or systemic disorders, and many drugs, including some antidepressants, can cause terrible itch as a side effect. There are few effective treatments for such intense and chronic itching, despite being a relatively common affliction: Eczema alone affects nearly 10 percent of people worldwide.

But good news may be on the horizon. A team of scientists, including faculty and students in the MBL Neurobiology Course, have identified a new gene that promotes itching, suggesting a way forward to a better understanding and, perhaps, to powerful new therapies.

Dr. Diana Bautista

MBL Neurobiology Course faculty member Diana Bautista of University of California, Berkeley. Credit: MarkJosephStudio.com

To identify genes that mediate itch, the team, led by Diana Bautista of the University of California, Berkeley, and Rachel Brem at the Buck Institute for Research on Aging, studied itch behavior across genetically distinct mouse strains.  Just as eczema and allergic itch can run in families, they found that some mouse strains were more likely to develop chronic itch and could pass this trait onto their progeny. They then compared gene expression levels in the itch-prone and itch-resistant mice, specifically in the sensory neurons that innervate the skin and mediate itch sensations.

They discovered that mice naturally expressing high levels of a particular gene, HTR7, were exceptionally itchy. This caught their attention, because HTR7 codes for a serotonin receptor, and “high levels of serotonin in the skin have long been known to correlate with itch severity in a variety of human chronic itch disorders,” Bautista says. They also discovered, in a mouse model of eczema, that activation of HTR7 triggered itch-evoked scratching while ablation of HTR7 significantly diminished itch.   

Some of the key work on the paper was done by three students in the MBL Neurobiology Course in 2014. Anne Olsen, Michael Kienzler, and Kyle Lyman worked with Bautista, a faculty member in the course, to identify some of the mechanisms by which activation of HTR7 promotes chronic itch signaling in the nervous system.  All three students appear as co-authors on the paper.

Understanding the molecular mechanisms underlying chronic itch is of significant clinical interest and there is much more to learn. “Abnormal behavior of three cell types mediate chronic itch,” says Bautista, “skin cells, neurons, and immune system cells. We want to discover the mechanisms that promote itch, and also what long-term changes in these cell types maintain chronic conditions.” In the meantime, the HTR7 receptor offers an exciting potential drug target for new medications seeking to sooth intense itchiness.

Citation: Morita T et al (2015). HTR7 Mediates Serotonergic Acute and Chronic Itch. Neuron, DOI: 10.1016/j.neuron.2015.05.044

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By Wallace Marshall
Co-director, MBL Physiology Course

Last month, I had a problem. I was teaching in the MBL Physiology course, using the giant, single-celled organism Stentor as a model system for students to learn quantitative approaches in cell biology. Stentor, which live in ponds, eat by creating a vortex of water that drags food into the cell’s mouth. The flow is created by thousands of cilia—tiny, hair-like cell parts that swing back and forth pushing fluid around. (Cilia are also critical for making the mucus in your airway flow away from your lungs, and patients with defects in these cilia can be really sick. So the question of how cilia make fluid flow is very important from a medical perspective. )

Stentor is a genus of large, trumpet-shaped ciliates, commonly found in freshwater ponds. Credit: EOL / micro*scope

Stentor is a genus of large, trumpet-shaped ciliates, commonly found in freshwater ponds. Credit: EOL / micro*scope

One of the students in our class, Shashank Shekhar from the CNRS Institute, France, had become interested in how the cell generates this pattern of fluid flow. Shashank started tracking the flow by putting small plastic beads into the water around the Stentor and then taking video images of the beads moving. This is a pretty standard approach in fluid dynamics called particle image velocimetry (PIV). But it’s not that commonly used in biology, and we didn’t entirely know what we were doing. The software we had been trying to use to track these particles didn’t give really nice flow lines. So this was the problem: How to use the flow of these tiny beads to figure out the pattern of flow around the cell as it feeds.

Frustrated by this problem, I decided to go get some coffee from Woods Hole Market. On the way back, I ran into my colleague Magdalena Bezanilla, an MBL Whitman Investigator from University of Massachusetts, Amherst, who works on cell biology. She thinks a lot about things moving inside cells so I figured I could get her input into our PIV challenge.

We ended up chatting about the problem in the MBL’s Waterfront Park, and while we were talking, a couple of guys emerged from the harbor in full scuba gear, carrying a huge metal bracket upon which was mounted a video camera and a laser. (This would be quite weird back home but it’s business as usual in Woods Hole.) I asked the guys what they were up to and they said they were using PIV to study the flow of fluid around ctenophores! Ctenophores or comb jellies are jellyfish-like animals that swim using cilia. So at the exact moment that we were pondering how to use PIV to track cilia-generated fluid flow in our single-celled organisms in the Physiology course, a guy walks out of the water and announces that he is doing the exact same thing, for comb jellies! (Those people who say that Woods Hole is a magical place are telling the truth.)

The guys with the scuba gear and lasers were Jack Costello of Providence College and Sean Colin of Roger Williams University, Whitman Investigators working for the summer at the MBL. Jack offered to give us advice about how to analyze our data, so I sent Shashank over to Jack’s lab in the Rowe building. With Jack’s help and expertise, Shashank was able to get beautiful flow lines from his data (see photo), which clearly reveal the pattern of cilia-generated flow around the Stentor cell while it feeds. Our big problem was solved in a single day due to a fortuitous combination of people, courses, coffee breaks, cells, beaches, marine organisms, and advanced technology. And that’s what summer at the MBL is all about.

Fluid flow around Stentor visualized through particle image velocimetry. Courtesy of Wallace Marshall.

Fluid flow around Stentor as it feeds, visualized by particle image velocimetry. Courtesy of Wallace Marshall.

Thank you to Wallace Marshall of the University of California, San Francisco, for contributing this post. All MBL scientists, students, community members, and visitors are invited to submit items for the MBL’s blog. Please contact Diana Kenney: dkenney@mbl.edu.

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By Laurel Hamers

The evolutionary path from single-celled organisms to complex species with higher-order thought processes has been mapped out with some degree of certainty, but how the earliest life forms appeared has proven a more difficult question. What conditions prompted organic molecules to assemble into the building blocks of life?

At the recent Origin of Life Symposium in Lille Auditorium, hosted by the MBL Physiology course, a panel of four distinguished scientists shared their research and opinions on this complex topic.

“What makes this a really important question is not only that it’s fundamental to how we understand biology as a process of living systems, but it’s also really important to how we think about the fate of this planet,” said Jennifer Lippincott-Schwartz, Physiology course co-director and a principal investigator at the Eunice K. Shriver National Institute of Child Health and Human Development.

Center of the Milky Way Galaxy IV – Composite. Credit:  NASA/JPL-Caltech/ESA/CXC/STScI - NASA JPL Photojournal: PIA12348.

Center of the Milky Way Galaxy IV – Composite. Credit: NASA/JPL-Caltech/ESA/CXC/STScI – NASA JPL Photojournal: PIA12348.

The first speaker, MBL Distinguished Scientist Mitchell Sogin, gave a broad overview of historical and current theories on the origin of life, with an emphasis on the role of geological diversity. Different geological microenvironments could have generated the building blocks that eventually combined to create habitable environments, he said.

Jack Szostak, Professor of Genetics at Harvard Medical School and 2009 Nobel Laureate in Physiology or Medicine, took the stage next. He described the problem as a step-by-step process.

“We’re not worried so much about defining exactly where life began,” he said. “I think what’s important is to understand the pathway. There’s a whole series of processes from simple chemistry to more complicated chemistry, building up the building blocks of biology,” Szostak said. “The goal for the field for the moment is to understand one continuous pathway from chemistry to biology.”

Nilesh Vaidya, a postdoctoral fellow at Princeton University, discussed research on spontaneous RNA assembly that he had carried out as a graduate student at Portland State University. By demonstrating that small RNA fragments can form cooperative networks that evolve toward greater complexity, he argued that early RNA-like molecules might have used a similar tactic to support the emergence of early life.

Tony Hyman, managing director of the Max Planck Institute of Molecular Cell Biology and Genetics, offered a different perspective, focusing on how cytoplasmic organization may have fostered an environment conducive to the formation of early life. He argued that phase separation of organic molecules due to cytoplasmic organization would concentrate these molecules in certain spaces and facilitate reactions that might not occur at lower concentrations.

A group discussion at the end helped symposium attendees to integrate the topics that the four researchers had presented.

The purpose of the symposium was not to reach a conclusion about the origins of life—the speakers all admitted that this was a daunting, and likely impossible, task. Rather, by bringing together eminent researchers in the field, the symposium organizers hoped to foster discussion between scientists addressing the same question from different angles.

 

Adam Cohen instructing in the MBL Physiology course in 2014.
Credit: Tom Kleindinst

Adam Cohen, a faculty member and former student in the MBL’s Physiology course, is one of three winners of the inaugural Blavatnik Awards for Young Scientists. The awards, given by the Blavatnik Family Foundation and the New York Academy of Sciences, honor exceptional young U.S. scientists and engineers. Each laureate receives $250,000 – the largest unrestricted cash prize for early-career scientists. Cohen is Professor of Chemistry and Chemical Biology and Physics at Harvard University, and a Howard Hughes Medical Institute (HHMI) investigator.

Cohen was recognized for “significant breakthroughs in cellular imaging that allow for the observation of neural activity in real-time, at single-cell resolution.” Combining his expertise in chemistry, physics, and biology, Cohen uses microscopy and lasers to develop noninvasive methods of visualizing and studying the roles of cellular voltage in neurons. His novel techniques, including fluorescent voltage indicators derived from microbial rhodopsins, help to answer questions about the propagation of electrical signals and could one day lead to the design of individualized treatments for conditions such as ALS, epilepsy, and bipolar disorders.

“Cohen is recognized as one of the nation’s most promising young scientists,” said Vern Schramm, Ruth Merns Chair in Biochemistry at the Albert Einstein College of Medicine and a member of the 2014 Blavatnik Awards National Jury.

The two other 2014 Blavatnik National Laureates are Rachel Wilson, Professor of Neurobiology at Harvard University and an HHMI Investigator, who was recognized for her research on sensory processing and neural circuitry in the fruit fly; and Marin Soljačić, Professor of Physics at MIT, recognized for his discoveries of novel phenomena related to the interaction of light and matter, and his work on wireless power transfer technology.

The Blavatnik Family Foundation is headed by philanthropist Len Blavatnik, founder and chairman of Access Industries, a privately held U.S. industrial group.

Neuroscientist Sheila Nirenberg, an alumna of MBL’s Neural Systems and Behavior (NS&B) course, was one of 24 people to be named a MacArthur Fellow this week by the John D. and Catherine T. MacArthur Foundation. Nirenberg, whose research focuses on deciphering the neural “codes” that transform visual stimuli into signals the brain can understand, is an associate professor in the Physiology and Biophysics department at Weill Cornell Medical College.

Nirenberg says NS&B, which she took in 1986, “was one of the best things ever. Worked hard,
played hard, learned so much so fast!” She also lectured in the MBL’s Methods in Computational Neuroscience course in 2012. MacArthur Fellows receive a no-strings-attached stipend of $625,000.

By Aviva Hope Rutkin

WOODS HOLE, Mass.–Back by popular demand, “Bodystorming,” a high-energy dance performance/demonstration presented by Black Label Movement of Minneapolis and the MBL Physiology course, will be held Sunday, July 21, in the MBL Club, 100 Water Street.The informal event, which is free and open to the public, is part of the MBL’s 125th Anniversary celebration. There will be two showings: 4 PM and 5:30 PM.

“Bodystorming” is an exciting new movement technique invented collaboratively by dancers and biologists that inspires powerful, athletic  dances as well as insight into cellular dynamics.

Over the past few years, Black Label Movement (BLM), directed by Carl Flink, has been collaborating with MBL Physiology course faculty member David Odde on “The Moving Cell Project.” By having the dancers physically represent cells and molecules, they are exploring the idea of “using dancers to literally embody our scientific hypotheses, in order to quickly convey them to other people,” says Odde, who is a biomedical engineer at University of Minnesota. “We call it bodystorming, which is like brainstorming ideas, but using actual bodies.”

Over the winter, the collaborators published an article, “Science + Dance = Bodystorming,” in Trends in Cell Biology. They also performed at a TED MED Conference. BLM is currently in residence in the MBL Physiology course, following up on a successful residency last summer.

“Bodystorming” is generously supported by the MBL Education Office, the MBL Associates, Larry Pratt and the Doherty Fund at Woods Hole Oceanographic Institution, and the University of Minnesota Institute for Advanced Study.

 

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Members of Black Label Movement in Woods Hole, Summer 2012. Credit: Dyche Mullins

 

 

What happens when graduate students in biology are given the freedom to play, dabble in new fields, launch into the unknowns of genuine research, not worry about getting “good” results?

In the case of the MBL Physiology course, one outcome has been—paradoxically—an extraordinary level of new knowledge and publications generated by student-and-faculty teams.

In the Dec. 21 issue of Science magazine, several scientists who have directed the Physiology course detail their winning formula for instilling in students the passion for and ability to conduct “real research,” as lead author Ron Vale of University of California, San Francisco, describes it.

The article presents the overwhelmingly positive feedback from a poll of Physiology course alumni from 2004 to 2010; and the remarkable list of 23 research papers and 59 meeting abstracts that developed out of Physiology course projects from 2005 to 2012.

Physiology course students, faculty, and family members with a sand sculpture they made of the mitotic spindle. Photo courtesy of Ron Vale.

Vale and Tim Mitchison of Harvard Medical School co-directed the Physiology course from 2004 to 2009 and revamped it in significant ways: (1) an equal number of students from cell biology and from physical sciences are admitted (2) students go through a “boot camp” to learn research techniques outside their fields and to begin thinking and stretching beyond their comfort zones (3) faculty give students the kernel of a “real” research problem – not an exercise – and the students develop an experimental plan, reporting back on what they found at the end of 11 intense days (often working 14 hours a day!)

And if they find nothing? Not a problem! “That’s most of what is going on!” Vale says. “Learning from failure is a crucial part of being a scientist.” The atmosphere the course intentionally creates is “intense, yet low-risk,” minimizing “the fear of failure or of appearing ignorant, factors that impede students, as well as senior scientists, from venturing into new fields or learning new approaches,” the article states.

Very often, students and faculty become so inspired by a research problem that they continue to work on it after the course ends, at their home institutions. That is how the seven-week Physiology course has generated so many publications.

The positive impact on students is evident from the alumni poll, which includes comments like, “I am now much more likely to try new experiments even though they seem nearly impossible. This attitude has had a very positive influence on the fun I have being a scientist, which is also reflected in the results.”

“People have a tremendous amount of fun in the Physiology course, whether their project gets a good result or not,” Vale says. “They appreciate the experience of going after a real research problem, of being surrounded by faculty and fellow students who are excited by the thrill of the chase … We are trying to learn something new, and we don’t necessarily know how to get there. That is science!”

The current co-directors of the Physiology course, Dyche Mullins of University of California, San Francisco, and Clare Waterman of the National Heart Lung and Blood Institute, have preserved the basic structure and spirit that Vale and Mitchison brought to the course.

Physiology is one of 22 courses the MBL offers for advanced, laboratory-based research training in fields such as cellular physiology, embryology, neurobiology, and microbiology.

Citation:

Vale RD, DeRisi J, Phillips R, Mullins RD, Waterman C, and Mitchison TJ (2012) Interdisciplinary Graduate Training in Teaching Labs. Science 338: 1542-1543.

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