MBL


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

The MBL’s collecting boat, the Gemma, has had a few passengers from Woods Hole Oceanographic Institution of late: Aran Mooney, a biologist, and Casey Zakroff, an MIT-WHOI Joint Program graduate student. Mooney and Zakaroff are studying the impact of ocean acidification on squid, using data they collected with the help of the Gemma’s captain and crew. (Ocean acidification is the ongoing decrease in the pH of the Earth’s oceans, caused by the uptake of carbon dioxide (CO2) from the atmosphere.)

Along with being a key species in the oceanic food web, squid have a multimillion-dollar impact on the human food industry. They are a vital component to the marine ecosystem’s wellbeing, as well as ours, making it crucial to monitor any risks that threaten healthy growth.

In the film, Is Ocean Acidification Affecting Squid?, produced by Daniel Cojanu, Mooney and Zakroff show how rising pH levels may be impacting a local and much prized marine species.

 

By Hunt Willard
MBL President and Director

It’s now been five days since the tragic earthquake struck Nepal. The official death toll has passed 5,000, but this doesn’t begin to tell the story of devastation in Nepal and neighboring regions of China and India that has affected millions of people in the region, wiped out entire villages, and destroyed ancient landmarks of cultural, religious and historic significance.

Kathmandu Valley, April 25. Credit: UNDP Nepal

Kathmandu Valley, April 25. Credit: UNDP Nepal

From the other side of the world, where we finally welcome spring to Woods Hole, it is difficult to grasp the scope of this disaster and the scale of suffering. This is why we tend to focus on specific events or images – the video of avalanches on Mt. Everest, or the neurosurgeon/journalist Sanjay Gupta performing brain surgery on an injured child, or a woman in Kathmandu who was pulled alive from the rubble, 36 hours after her 5-story apartment building came crashing down on top of her. Those images help us stay connected to the story, but ultimately fail to convey the massive scale of suffering, when three stories so quickly blur to become 3,000 and then 3 million.

Science – no less than the world around us – is increasingly a global enterprise. This is especially so at the MBL, where we regularly welcome scientists, staff, students and visitors from around the world.

And this is why we should pause – even for just a moment – to think about our colleagues and friends, some of whom, even unknown to us, have relatives, extended family members, classmates or neighbors who come from Nepal and the regions so affected by this tragedy. Today, we can all be Nepalese, and they can all be part of the MBL community.

Thank you for your thoughts and for what you do.

 

 

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By Diana Kenney

The startling discovery of a contagious cancer in steamer clams, published this week in the journal Cell, had its origins at the MBL.

Carol Reinisch began studying a fatal, leukemia-like disease of soft-shell clams (Mya arenaria) at the MBL in the mid-1970s, when it was causing major die-offs among distinct bivalve populations. This week, scientists announced that the disease is a contagious form of cancer that has been transmitted between clam populations from New York to Prince Edward Island, Canada. The study was conducted by Michael Metzger and Stephen P. Goff of Columbia University, Jim Sherry of Environment Canada, and Reinisch.

The soft-shell "steamer" clam, Mya arenaria. Photo by Scott Bennett, MBL

The soft-shell “steamer” clam, Mya arenaria. Photo by Scott Bennett, MBL

Infectious cancer (or “super metastasis”) is known in only two other instances in nature: as a venereal disease in dogs and as a facial tumor in Tasmanian devils, according to an article about the clam leukemia in Science.

Reinisch, a few years ago, thought the clam disease might be caused by a virus, and she brought it to Goff’s attention. Metzger and Goff, she says, “conducted the truly elegant molecular biology to show the cancer is externally derived.”

Through genetic analysis of numerous sick clams, the team showed that while their cancer cells were nearly identical, the cancer cells did not match the genomes of their host clams. This indicates the cancer cells likely descended from a single, original clam cell “gone rogue,” which then multiplied and spread to nearby clams. How the disease was transmitted is still unknown.

Steamer clams are eaten by human beings and are an important commercial fishery. However, researchers say there is no health risk to humans who eat diseased clams. “Nobody eats them raw. When you steam or boil them, it kills all the cells,” Reinisch says.

Reinisch has studied this clam and bivalve disease for decades because “it’s one of the best and unique models of carcinogenesis in nature that we have,” she says. She carried out research at MBL for more than 30 years, first as a Whitman summer investigator and then, from 1998 to 2005, as a year-round scientist. She moved her lab to the MBL in order to explore Mya arenaria as a model system for cancer. Formerly, she was a Department Chair of Comparative Medicine at Tufts Veterinary School.

Reinisch’s earlier work indicated that the spread of the clam leukemia has an environmental component. “For whatever reason, the [cancer] transmission seems to be easier in stressed areas,” she says. “When we used to collect clams in New Bedford, Mass., we knew exactly where to find the ones with leukemia. The clams in a PCB contaminated site were much more liable to have the disease.”

Currently, Reinisch collaborates with Environment Canada in Burlington, Ontario, and is identifying the range of this transmissible cancer. She has studied bivalves as far north as Alaska and the Arctic and hopes to conduct field research in Antarctica in the coming year.

Citation:

Metzger, MJ, Reinisch C, Sherry J, and Goff SP (2015) Horizontal transmission of clonal cancer cells causes leukemia in soft-shell clams. Cell 161: 255-263.

 

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 www.hamiltonthorne.com/index.php/oosight-overview.

 

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