Dear Colleagues and Friends,
The tragic circumstances surrounding the killing of George Floyd in Minneapolis, and a number of other recent acts of racially motivated violence painfully remind us that for too long we have ignored the systemic discrimination and unjust bias that plagues our nation. We recognize the pain this brings to all in our community, particularly those who live with the knowledge that the color of their skin unjustly makes them a target of hate.
We are seeing the cumulative anguish and frustration from generations of racial disparity and systemic oppression in our country manifested in the solidarity of peaceful protest. At this moment in our history, it is essential that we reaffirm and embrace the core values of the MBL. Every individual on our campus must be treated with dignity and respect in a safe and comfortable work and learning environment. As a community we must not tolerate racism and social injustice. We commit ourselves to combating these injustices by creating a climate focused on equity, civility, respect, and safety for all individuals in our MBL and Woods Hole community. These lofty ambitions take great effort. As an institution we are working to understand how best to make these changes, and welcome input from the members of the MBL community.
Despite our physical distance at this time, we ask you to support one another in a shared commitment to creating the most inclusive and diverse community that we possibly can – one that fosters trust and values and encourages the contributions and perspectives of every one of its members.
Thank you for your attention to this serious issue and for your commitment to our shared values.
Sincerely,
Nipam H. Patel, Director
Adam Carter, Director, Office of Sponsored Programs and Research Administration
Alison Crawford, Chief of Staff
Ann Egan, Director, Human Resources
Mary S. Harrington, Director, Finance
Gina Hebert, Director, Communications
Scott Koerner, Director, Information Technology
Sebastien Laye, Chief Advancement Officer
Linda Hyman, Burroughs Wellcome Director of Education
David Mark Welch, Director of Research; Co-Chair, MBL Diversity and Inclusion Advisory Committee
Jennifer Morgan, Director, Bell Center for Regenerative Biology & Tissue Engineering; Chair, MBL Diversity and Inclusion Advisory Committee
Marie Russell, Director, Facilities and Services
Paul Speer, Chief Operating Officer
Jennifer Walton, Director, Library Services; Co-Director, MBLWHOI Library
Contact: dkenney@mbl.edu; 508-685-3525
WOODS HOLE, Mass. -- Amyotrophic lateral sclerosis (ALS) is one of the most devastating adult-onset neurodegenerative diseases. Patients, including the late actor/playwright Sam Shepard, become progressively weaker and eventually paralyzed as their motor neurons degenerate and die.
Yuyu Song at the Marine Biological Laboratory.
To find a cure for ALS, which is fatal, scientists need a deeper understanding of how it interrupts motor neuron communication channels. Because motor neurons reach from the brain to the spinal cord, and from the spinal cord to the muscles, when they die, the brain can no longer initiate muscle movement.
Yuyu Song of Harvard Medical School was a Grass Fellow at the Marine Biological Laboratory (MBL) when she took advantage of a powerful research organism in neuroscience, the local squid, to start asking how a mutant protein associated with familial ALS behaves under controlled conditions.
Her study, recently published in eNeuro, clarifies the mechanisms underlying neural dysfunction in ALS, and also suggests a novel approach to restoring the health of motor neurons in patients with the disease.
Restoring neurotransmission
Song focused on how this mutant protein, called G85R-SOD1, affects neurotransmission at the squid “giant synapse,” the junction where neurons transmit chemical signals to muscle fibers, causing the muscle to contract. The squid giant synapse is one of the few mature nervous systems that mimics human neuromuscular junctions, while allowing precise experimental manipulations and live measurements.
Song showed that the presence of misfolded mutant SOD1 inhibits synaptic transmission and diminishes the pool of synaptic vesicles, whose job is to deliver neurotransmitters critical for neuronal connections.
Surprisingly, synaptic function was restored by intermittent, high-frequency stimulation, which suggested aberrant calcium signaling may underlie SOD1 toxicity to normal synaptic transmission. To test this hypothesis, Song used calcium imaging to capture the abnormal calcium influx in the presynaptic terminal and confirmed the protective role of a calcium chelator, which corrected the calcium imbalance without affecting neurotransmission.
This suggests a new approach to therapeutic intervention for ALS, in which chemical or electrical regulation of calcium and its downstream signaling pathways may restore the health of motor neurons.
A catch of the Woods Hole squid, Doryteuthis pealeii, aboard the MBL collecting boat, The Gemma. Credit: Daniel Cojanu
“Altogether, our results not only demonstrated synaptic dysfunction related to ALS and its underlying molecular pathways, but also extended our understanding of fundamental synaptic physiology,” Song says.
Developing a novel disease model - and finding a family
Song, who is an MD-PhD, has spent numerous summers at the MBL using the local squid to unravel the basic pathologies underlying neurodegenerative disease. She started coming regularly in 2007 as a graduate student with Scott Brady, whose lab was developing the squid’s giant axon (nerve fiber) as a system for studying human disease.
“One summer, I chatted with Rodolfo Linas at the MBL, who has been doing synaptic recordings in the squid for many decades,” Song says. “I helped his lab with some electron microscopy on the squid giant synapse together with Jorge Moreira, and Rodolfo challenged/encouraged me to do synaptic studies myself. In the summer of 2013, I decided to establish the squid giant synapse as a disease model for ALS and to learn electrophysiology in this classical preparation.”
That same summer, Song met Whitman Center scientists Steve Zottoli, George Augustine and Len Kaczmarek, who advised her to apply for a Grass Fellowship, in which she could set up an independent research project at MBL. After her productive Grass Lab experience, Song returned to the MBL for several years as a Whitman Center scientist and initiated further collaborations with MBL and University of Chicago scientists.
Song found an enduring family at the MBL, she says. “The 2014 Grass Fellows are still in touch with one another and we share our success and struggle in life and science together,” she says. The Grass Lab’s directors and administrators remain dear friends. And she is quick to acknowledge the essential contribution of the MBL’s collecting operation, which provides a daily catch of squid to her and other MBL scientists in season. “All the crew in the Marine Resources Center feel like family, not just scientific collaborators,” she says.
Currently, Song is an instructor in neurology at Harvard Medical School and Massachusetts General Hospital. And she is waiting – like so many researchers –for the green light to return to Woods Hole!
Citation:
Song, Yuyu (2020) Synaptic Actions of Amyotrophic Lateral Sclerosis-Associated G85R-SOD1 in the Squid Giant Synapse. eNeuro, DOI: 10.1523/ENEURO.0369-19.2020
Homepage image: The longfin inshore squid (Doryteuthis pealeii). Credit: Roger Hanlon
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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery – exploring fundamental biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago.
Contact: dkenney@mbl.edu; 508-685-3525
By Emily Greenhalgh
A little skate (Leucoraja erinacea) hatchling (left) with a skeletal preparation of a little skate hatchling (right), with cartilage stained blue and mineralized tissues stained pink. Credit: Andrew Gillis
WOODS HOLE, MASS. — Nearly a quarter of Americans suffer from arthritis, most commonly due to the wear and tear of the cartilage that protects the joints. As we age, or get injured, we have no way to grow new cartilage. Unlike humans and other mammals, the skeletons of sharks, skates, and rays are made entirely of cartilage and they continue to grow that cartilage throughout adulthood.
And new research published this week in eLife finds that adult skates go one step further than cartilage growth: They can also spontaneously repair injured cartilage. This is the first known example of adult cartilage repair in a research organism. The team also found that newly healed skate cartilage did not form scar tissue.
“Skates and humans use a lot of the same genes to make cartilage. Conceivably, if skates are able to make cartilage as adults, we should be able to also,” says Andrew Gillis, senior author on the study and a Marine Biological Laboratory Whitman Center Scientist from the University of Cambridge, U.K.
The researchers carried out a series of experiments on little skates (Leucoraja erinacea) and found that adult skates have a specialized type of progenitor cell to create new cartilage. They were able to label these cells, trace their descendants, and show that they give rise to new cartilage in an adult skeleton.
Why is this important? There are few therapies for repairing cartilage in humans and those that exist have severe limitations. As humans develop, almost all of our cartilage eventually turns into bone. The stem cell therapies used in cartilage repair face the same issue—the cells often continue to differentiate until they become bone. They do not stop as cartilage. But in skates, the stem cells do not create cartilage as a steppingstone; it is the end result.
“We’re looking at the genetics of how they make cartilage, not as an intermediate point on the way to bone, but as a final product,” says Gillis.
The research is in its early stages, but Gillis and his team hope that by understanding what genes are active in adult skates during cartilage repair, they could better understand how to stop human stem-cell therapies from differentiating to bone.
Note: There is no scientific evidence that “shark cartilage tablets” currently marketed as supplements confer any health benefits, including relief of joint pain.
Citation: Aleksandra Marconi, Amy Hancock-Ronemus and J. Andrew Gillis (2020) Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea. eLife, DOI: https://doi.org/10.7554/eLife.53414
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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery – exploring fundamental biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago.
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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery – exploring fundamental biology, understanding biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago.