Archive for June, 2013

ZIP12 RNA marked with blue dye in a frog brain. Credit: Mark Messerli, MBL

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For Immediate Release: June 27, 2013
Contact: Diana Kenney, Marine Biological Laboratory
508-289-7139; dkenney@mbl.edu

WOODS HOLE, Mass.– A new study helps explain how parts of the brain maintain their delicate balance of zinc, an element required in minute but crucial doses, particularly during embryonic development.

The study, led at the Marine Biological Laboratory (MBL) by Mark Messerli in collaboration with scientists from the University of California, Davis, shows that neural cells require zinc uptake through a membrane transporter referred to as ZIP12.. If that route is closed, neuronal sprouting and growth are significantly impaired and is  fatal for a developing embryo. Their discovery was published in the Proceedings of the National Academy of Sciences.

“This particular transporter is an essential doorway for many neurons in the central nervous system,” explains Messerli. “You knock out this one gene, this one particular pathway for the uptake of zinc into these cells, and you essentially prevent neuronal outgrowth. That’s lethal to the embryo.”

Previously, scientists thought that zinc could use more than one pathway to enter the cell during early brain development. Some other elements, like calcium, enjoy such luxury of multiple options.

Knocking out ZIP12, affected several critical processes in the brain, the scientists found. For example, frog embryos were unable to develop their neural systems properly. Additionally, neurons had trouble reaching out to connect to other neurons; their extensions were both shorter and fewer in number than normal.

“We were surprised that ZIP12 was required at such an early and critical stage of development,” said Winyoo Chowanadisai, a researcher in nutrition at the University of California at Davis and visiting scientist in the Cellular Dynamics Program at the MBL. Dr. Chowanadisai was the first on the team to realize that ZIP12 is expressed in such abundance in the brain.“This study also reinforces the importance of periconceptional and prenatal nutrition and counseling to promote health during the earliest stages of life.”

ZIP12 is part of a larger family of transporters involved in the movement of metal ions from outside the cell. Other reports showed that simultaneously blocking 3 other transporters in the family – including  ZIP1, 2, and 3 – had no major effects on embryonic development.

Zinc is needed for healthy neural development, helping the brain to learn and remember new information. However, too much zinc can also be problematic.

The research team is investigating the implications of their results on processes like embryonic brain development and wound healing.

“[The result] was not expected,” said Messerli, a physiologist in the MBL’s Bell Center for Regenerative Biology and Tissue Enginering and Cellular Dynamics Program. ““We found that zinc uptake through ZIP12 is a regulatory point for neuronal growth, required for development and possibly required for learning and memory throughout life. We want to elucidate the downstream targets that zinc is affecting. That’s the next exploration.” 

— Written by Aviva Hope Rutkin

Photo Caption

ZIP12 RNA marked with blue dye in a frog brain.

Citation

Chowanadisai W, Graham DM, Keen CL, Rucker RB and Messerli MA (2013) Neurulation and neurite extension require the zinc transporter ZIP12 (slc39a12). PNAS 110: 9903-9908.

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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 1888 in Woods Hole, Massachusetts, the MBL is an independent, nonprofit corporation.

 

Nobel Prize winner Rod MacKinnon had his lunch table rapt.

He was describing a kayaking trip he’d taken a few years earlier. After flipping his boat right-side-up to correct an accidental roll, MacKinnon discovered that he’d narrowly missed sharing the water with a six-foot shark. He watched, frozen in place, as the beast hunted down an unlucky seal. As MacKinnon relayed the tale, graduate students stared at him from around the table, their mouths agape.

This anecdote marked the end of MacKinnon’s annual visit to the MBL’s Neurobiology course to lecture about his area of specialty, potassium channels. The class, which features lectures from numerous visiting scientists, is co-directed by UCSF’s Graeme Davis and Cornell’s Timothy Ryan.

“I love coming back here,” MacKinnon said. “It’s a nice opportunity to teach [students] about your own field and maybe turn on some bright scientists to the stuff you like.”

MacKinnon has been around the MBL for “my whole career,” he says. He first visited the MBL as a post-doc in 1985, shortly after he had decided to pursue a career in research rather than medicine. One of his former professors, Brandeis biochemist Chris Miller, invited MacKinnon to help teach a two-week section on electrophysiology.

Since then, MacKinnon has become internationally recognized for his work on potassium channels, the pathways that potassium ions use to enter the cell. The concentration of such ions inside the cell is crucial in the regulation of many different functions, including neuron firing. In the late 1990s, MacKinnon’s laboratory discovered the structure of these channels using X-ray crystallography. This research helped to explain why the channels admitted potassium ions while blocking much smaller sodium ions. MacKinnon was awarded the Nobel Prize in Chemistry for this work in 2003.

MacKinnon’s Neurobiology lecture at the MBL this year followed the arc of scientific discovery. Using handwritten slides, MacKinnon walked the students through the different questions that scientists had faced when studying these elusive channels. How did they know that the channels were there? How might they divine how the channels functioned? Was there an upper limit on how much potassium could move through at a given time?

“I find it’s easy to learn science if you know the questions that people were faced with at the time,” he explained. “Once it’s all figured out, the synopsis is made and then that’s what future generations learn. But sometimes that synopsis by itself is harder to understand out of the context of the questions at time, so it’s nice to trace the history of how something came to be understood. Once you know that, it’s much easier to understand the concept, and much easier to remember.”

After the lecture, MacKinnon followed the students to lunch at Swope, where they chatted about his views on science and the different research projects the students were involved in. He also shared some his favorite places in the area to grab a bite – and to go kayaking.

“It’s a great honor to see a Nobel Laureate speak,” said Cliff Woodford, a chemistry graduate student from UCSD. “It makes you feel like what you’re doing is important when you get to see the giants in the field.”

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A screenshot of the live-stream on Friday, June 21.

A screenshot of the live-stream on Friday, June 21.

This afternoon, MBL microbial oceanographer Julie Huber took an enthralled audience at MBL on a dive to the bottom of the sea, via a livestream video on YouTube. If you missed it, there are more opportunities to tune in this week!

Huber is part of an international team of scientists aboard research vessel R/V Falkor, operated by Schmidt Ocean Institute. The Falkor is spending June at the Mid-Cayman Rise, an ultraslow spreading ridge at one of the deepest points of the Caribbean Sea (about 4 miles down). At 6 AM ET/3 AM PT every day until June 29, the team will air live footage of their explorations along the ridge.

The team, which is led by Chris German of Woods Hole Oceanographic Institution, is focusing on two new hydrothermal vent fields, Europa and Walsh, during this expedition. These vents are cracks along the bottom of the ocean that form when the Earth’s plates shift. The scientists are studying the vents from biological, chemical, and physical perspectives to learn more about these dynamic geological formations and the extreme life they host.

Huber studies microbial life around the vents. She is interested in learning more about how the bacteria and Archaea can thrive in the harsh, hot conditions of the Mid-Cayman Rise. (Huber will continue this work on another Falkor cruise that she is leading this fall.)

The team uses an unmanned vehicle, HROV Nereus to explore the floor in-depth. Their live-stream video will be captured on the same cameras used by James Cameron’s DEEPSEA CHALLENGER submersible on its 2012 dive at the Mariana Trench.

Tune in tomorrow at 6 AM EST to the Schmidt Ocean Institute’s YouTube channel to watch the next Nereus dive live. (Dives may be delayed due to technical issues. Schedule updates are posted here.)

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By Aviva Hope Rutkin

Visiting scientist Guillermo Yudowski wants to make sea anemones happy.

Every morning, he arrives at his MBL laboratory and looks into a group of plastic tanks. Inside are samples of Aiptasia pallida, a hardy strain of anemone found in abundance near the University of Puerto Rico, where Yudowski conducts neurobiological research. Happy A. pallida, he says, are “colorful and open”; sad ones are closed and white. The white samples are near death and will only last three to four days in their containers.

Top view of a day-old spawned Porites spp. coral larvae. Composite image seen under a fluorescent microscope. Symbiotic zooxanthellae autofluorescence in red, larvae epidermis autofluorescence in green. Courtesy of Guillermo Yudowski.

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Turning white—becoming, in Yudowski’s words, “sad”—is called bleaching. The anemone’s tissues are home to zooxanthellae, vibrant photosynthetic algae that produce food for the anemone and give it a characteristic brown color. Bleaching expels this algae from their home. The bleaching process is thought to be triggered by stress: a decrease in light availability, for example, or changes in the water’s temperature or pH. And these changes don’t need to be dramatic. A difference of a couple degrees Celsius can be enough to effectively bleach an anemone.

Yodowski and his colleagues hope their research will point to a cost-effective treatment for bleaching, which poses a serious threat not only to anemones, but to the world’s coral reefs. Though anemones and corals are different, strategies that work for the one organism may be effective for another. The changing climate has already led to mass bleaching events in the Great Barrier Reef, as well as coral reefs in the Indian Sea, the Caribbean Sea, and the Florida Keys.

“If you read the literature, some say that all the coral is going to die in 50 years. Others say, maybe 50 to 100,” says Yudowski. “It doesn’t make a big difference.”

To move toward a solution, Yudowski wants to understand what’s happening to the anemones on a microscopic level. If we figure out why bleaching occurs on a cellular level, then perhaps we can discover how to stop it from happening altogether.

“We don’t really know much about the basic molecular mechanics of the process,” explains Yudowski. “We are trying to understand how stresses like increased ocean temperature and acidification induce the expulsion of the algae.”

Yudowski and his student, Michael Marty-Rivera, are treating anemones with antioxidant compounds found in red wine and green tea. Previous research shows that reactive oxygen species, a kind of chemically reactive molecule, can trigger the bleaching process. Yudowski and Marty-Rivera think that these antioxidants might be able to counteract the effects of these trigger molecules. They will test the efficacy of their treatments by measuring the amount of photosynthetic activity in the anemones, as well as the number of zooxanthellae present.

Yudowski and Marty-Rivera will spend two months at the MBL this summer before returning to the University of Puerto Rico where, in close collaboration with Professors Loretta Roberson and Joshua Rosenthal, they run several different coral research projects. They want to understand the mechanism of calcification in corals and how environmental variables, such as temperature and pH, impact corals’ ability to form reefs and maintain a healthy symbiosis with their zooxanthellae partners.

Funding for the research is provided by the Puerto Rico Center for Environmental Neuroscience and the National Science Foundation Center of Research Excellence in Science and Technology.