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Joe DeGiorgis
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MBL Launches Squid Genome Project
With a recent Nobel Prize under its belt and a project underway to sequence many of its genes, it seemed like the surf clam might be gaining on the squid in the ongoing rivalry for the most famous MBL research model. But the newly launched Squid Genome Project aspires to keep the race close, to enhance the squid’s reputation as an important model for the study of human disease, and to lure new researchers to the squid and Woods Hole.
The project, which aims to identify the long-finned squid’s (Loligo pealei) key genes, saw its first results in August. “To date, we’ve identified more than 3,000 genes out of what we predict will total approximately 35,000 genes,” says MBL/NIH neuroscientist Joe DeGiorgis, who is co-directing the project with MBL Whitman Investigator J. Peter H. Burbach of the Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht in the Netherlands.
“We are focusing on neuronal genes expressed in one of the major neural centers of the squid. The genes that are emerging from this project are providing a wealth of new information concerning mechanisms of neuronal development and regulation,” says Burbach. “It is an exciting phase. We have already seen surprises and more may come up during further expansion of the data.”
Initiated with funding from the Laboratory of Neurobiology at NIH and the Netherlands Brain Foundation HsN, the project unites squid researchers from around the world, as well as researchers who are searching for certain genes in the squid.
“Scientists hoping to understand neurological diseases by studying squid have reached the point where they need genetic information,” says DeGiorgis, who uses squid to study a protein involved in Alzheimer’s disease called Amyloid Precursor Protein with his Brown University collaborator Elaine Bearer. DeGiorgis is also working with Tom Reese of the NIH to learn how intercellular cargoes are trafficked within the axon.
Squid Genome scientists are particularly interested in the genes responsible for nervous system functions so they can better understand related medical problems. “Knowing who the players are will help us to figure out how they work and vastly increase the rate at which we make our discoveries,” says DeGiorgis. It is also the first step on the long road toward finding targets in nerve cells that might be used for drug research.
Another goal is to help scientists studying genes associated with certain diseases confirm that the genes are common to both squid and humans. Such information could help them decide whether using squid would serve their research interests.
“There are many examples of scientists looking for specific genes in squid nerve cells,” says DeGiorgis. “Without genomic data, finding this information is time consuming and labor intensive. It’s like trying to find a needle in a haystack.”
DeGiorgis says one of his biggest hopes for the project is that it will interest up-and-coming scientists in working on marine models and, in turn, lure them to Woods Hole. “Hopefully the efforts to sequence the genomes of both the clam and squid will reestablish them as premiere research models and bring new researchers to the MBL,” he says.
In fact, recent results from the first round of lab work have identified genes associated with Huntington’s, Niemann-Pick, and Alzheimer’s diseases and are already informing scientists working on these illnesses.
For example, Stephen Sturley, a researcher in the pediatrics department at Columbia University Medical Center is now considering using the squid in his research on Niemann-Pick disease. “At the MBL last summer we performed some preliminary neurotransmission experiments with George Augustine [of Duke University Medical Center] using a drug that induces a Niemann-Pick type C disease state,” says Sturley. “There was a suggestion that the drug had some effect on the squid giant axon, and Joe’s observations that the genes are conserved in the squid led us to further believe this organism might be a good model to study the mechanisms of this disease.”
So far, most of the information being generated by the Squid Genome Project is spreading by good old-fashioned word of mouth. Soon, though, DeGiorgis hopes to publish it on a website for easy and quick access.
DeGiorgis and Burbach report that things are progressing well at this early stage, but admit they have a long way to go. “It’s a good beginning, but it’s the tip of the iceberg, and completing the project is money dependent,” says DeGiorgis. The project’s goal, he says,$3 to $5 million and sequence all of the genes.
Unraveling the squid genome is critical to scientists who use, or want to use, the squid in their research. “Identifying the genes of research animals enables scientists to push forward at a much faster rate,” DeGiorgis says. “I can’t adequately say how much power you have when you have genomic information, and this is absolutely where the MBL should be heading.”
Stuck on Squid
Facts about the long-finned squid and the MBL:
- For more than 70 years, MBL scientists have been studying the squid to learn how the nervous system works.
- The fibrous part of the squid nerve cell, or giant axon, was originally described by L.W. Williams, working at the MBL, in 1909 and reconfirmed by J. Z. Young in the 1930s.
Young introduced this ideal model system to his MBL colleague K.S. Cole, who in 1937 used it to make the first measurements of the resistance changes underlying the nervous impulse. This unique preparation later served as the basis for the elegant analysis of the action potential by Alan Hodgkin and Andrew Huxley, who used the voltage clamp technique they had learned from Cole at the MBL. Hodgkin and Huxley won the Nobel Prize in 1963.
- The squid giant synapse was discovered by Bullock and Hagiwara (1968) at the MBL and continues to be exploited at MBL and elsewhere for elucidating the mechanisms of synaptic transmission.
- Over the course of his career, MBL squid collector Henry Klimm netted more than 800,000 squid for study by MBL scientists. He retired this year at the age of 90.
- Forty-one researchers from across the U.S., as well as Italy, the Netherlands, Venezuela, and Argentina, used squid in their research this past summer at the MBL. In recent years, several MBL scientists, including Clay Armstrong and Ron Vale, have made significant biological discoveries with squid models.
- Today, squid research is important to understanding numerous diseases, including Alzheimer’s, Niemann-Pick, Multiple Sclerosis, Cystic Fibrosis, Amyotrophic Lateral Sclerosis (ALS), Parkinson’s, and Huntington’s.
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