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:

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:

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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.

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