Langford's studies of squid nerves may advance understanding of human system

Posted 06/30/01

Each summer since 1972, Dartmouth Professor George Langford has gone to Cape Cod to conduct neurological research at the Marine Biological Laboratory (MBL) in Woods Hole, Mass. This locale is ideal, as the waters of the Atlantic provide Langford with the tools of his trade: live squid.

"I've been studying the neuron transportation system for many years, and I'm always excited each summer to begin my field research," said Langford. He examines how chemical signals are carried along nerve cells. These chemicals are important for the passing of electrical signals that deliver messages throughout the nervous system. Langford specifically studies the molecular motor proteins that bind to and transport the message-carrying particles along the nerve.

The molecular motors running along the neuron can carry viruses through the body, so understanding the mechanics better should lead to more effective treatment of the herpes virus, for example. And, when these motors break down, neurodegenerative diseases, such as Alzheimer's, may result.

Squid are particularly suited for this research because they have large, easily accessible nerve fibers, called giant axons. At just a half millimeter in diameter, the squid axon is just below human visibility, but it's much larger than a human axon.

This summer Langford and his research student, Kyle Simonetta '02, will meet the fishing boats every afternoon for freshly caught six inch- to foot-long squid, Loligo pealii. From the moment the squid are in the lab, the researchers have a short window of time to conduct their work.

"We get back to the lab, and immediately begin the dissection to remove the axon," explained Langford. "We then remove the membrane from the nerve to reveal the axoplasm." It's this material that contains the highway where materials are transported. The dissection takes about 30 minutes, and the resulting naked axoplasm lasts another hour and a half before it dies.

Langford and Simonetta will work with two or three squid each evening and go through about 100 before the summer is out. The researchers don't stop with the axon, however; the rest of the squid is not wasted. Langford says that after the giant axon is removed, you can still enjoy the calamari. It's an opportunity for the students to flex their culinary muscles while conducting research.**

During past summers at MBL, Langford and his students have learned that motor proteins myosin V and kinesin transport endoplasmic reticulum (ER), an intracellular body that regulates calcium, along the axoplasm. They have also discovered that during the journey, ER travels along both actin filaments and microtubules, the roadways of the axoplasm. This summer, Langford and Simonetta will work to discover the mechanism that coordinates and regulates transport. They will test the hypothesis that myosin V and kinesin act sequentially to move the ER along the neuron. They also hope to learn how these motor proteins transition from the actin filaments to the microtubules.

"I'm a biophysical chemistry major," said Simonetta, a native of Upton, Mass. "I was looking for a way to turn my classroom experience into hands-on experience, and this is it. So far I've learned to take out a giant axon and to isolate the optic nerve to get the myosin V." Simonetta confessed that he hadn't dissected anything since he was in the seventh grade. "Once I've learned the basics, maybe I can start my own research project later this summer."

This summer, Langford's lab is supported by the Josiah Macy Jr. Fellowship from MBL, and also is funded by a research grant from the National Science Foundation.

**Recently, Langford's lab voted 1998 Dartmouth graduate Brad Molyneaux's calamari recipe their all-time favorite. Molyneaux worked with Langford during the summers of 1998 and 1999. Instructions for "Dartmouth Calamari:" After the squid is cleaned and rinsed (about 1 1/2 pounds), soak it in milk overnight in the refrigerator. When you're ready to cook, cut the squid into rings, and dip into mixture of two eggs beaten together with 1/4 cup of water. Then dip into a mixture of 1/3 cup of flour, 1/3 cup of corn meal, 1/3 cup of bread crumbs, with a pinch each of salt, pepper and rosemary. Deep fry in hot oil for about 30 seconds; drain on filter paper.

Serve with a dip made by blending together one finely chopped roasted red pepper, a chopped dill pickle (kosher), a cup of mayonnaise, two teaspoons of Worcestershire sauce, a pinch each of dill, paprika, pepper, rosemary and salt.