March 14, 2006

Lessons of the Sea Urchin

Sea Urchins Harbor Active Immune Systems: Landmark Discovery May Hold Clues to Immunity in Higher Vertebrates


The world’s oceans hold many surprises. Just ask L. Courtney Smith, associate professor of biology at GW, whose recent discovery that sea urchins harbor active immune systems has sparked great excitement in the biological world.

Smith, who came to GW as an assistant professor in 1995, published research findings in April 2005 revealing that the immune system of the purple sea urchin produces a surprisingly large number of similar but diverse proteins when threatened by infection. She and her colleagues injected sea urchins with a bacterial cell wall fragment, triggering a complex response in the sea creature’s immune systems. Sea urchins — invertebrates (animals without a backbone) found at the lowest level of the lineage of animals culminating in mammals — have a similar early developmental process to humans, according to Smith, and that’s one of the reasons why they are distantly related to us. The colorful creatures — enclosed in thin brittle shells covered with movable spines — may, therefore, hold important clues to the evolution of immunity in higher vertebrates, including humans.

“Identification of novel mechanisms for generating immune diversity in invertebrates, which has implications for innate immune capabilities in all animals, may result in a better understanding of innate immunity in higher vertebrates,” Smith concluded in a paper on the findings, in the April 2005 issue of Physiological Genomics.

Smith’s discoveries about sea urchins shed important light on how invertebrates cope so well in their pathogenic environment. “The big surprise in our findings is that it is evolutionarily significant that animals other than vertebrates have mechanisms, most still unknown, to diversify their innate immune systems to address the problem of microbes always finding new ways to infect,” she states. “It turns out that we and other vertebrates aren’t unique in that. Probably all animals and plants do this, but we never even thought of asking that question before.”

Smith says her research forges a greater understanding of how animals without adaptive immune systems can still protect themselves from infection. “We’re beginning to appreciate that sea urchins may use genes that are different from antibodies, and probably have different mechanisms from humans to diversify those genes, and are able to produce an array of proteins with lots of diversity,” she says.

According to Smith, when sea urchins detect they are infected with bacteria, they experience reactions similar to mammals.

“Mammals and higher vertebrates make the vast number of antibodies necessary to respond to and protect us from all potential pathogens that we may run into,” she explains. “The mammalian immune system is designed to keep ahead of the pathogens. The revolutionary thing is that animals without antibody genes, like the sea urchin, appear to be using different gene systems and mechanisms to do the same thing — to recognize and perhaps even kill all possible pathogens.”

This recent discovery builds upon Smith’s two decades of research focusing on the immune systems of marine invertebrates. “I got interested in marine biology at the age of six, when I went to the ocean for the first time and saw my first sea anemone,” she says. When immunology sparked her interest after earning her master’s degree, Smith decided to combine the two fields, earning a PhD from the University of California, Los Angeles in 1985. Just before arriving at GW, she made a landmark finding.

“A long time ago, scientists discovered that there was a set of proteins called the complement system that work with antibodies to kill bacteria,” explains Smith. “It was always assumed that the complement system and antibodies worked together, so I was astounded to discover that a complement system functioned in sea urchins in the absence of antibodies. This was revolutionary, as we had always thought that antibodies came first during evolution for recognizing bacteria and the complement system came along afterwards. Now, we realize that it’s actually the other way around.”

Smith’s work could potentially hold broad implications for how immune systems function in higher-level animals. “There may be gene systems in mammals that have other ways to scramble and diversify themselves that we haven’t yet thought to look for,” she states. “After completing our investigation of the sea urchin’s immune system, we may find it worthwhile to go back to the mammalian system to further our understanding of how that immune system functions.”

While Smith is quick to state that it’s still very early in her research, she speculates that a thorough understanding of the sea urchin’s immune system may eventually lead to medical applications if it’s proven that the invertebrate’s simple immune system uses scrambling mechanisms that can be identified in humans.

For now, one thing is certain. “There’s a lot more going on than we thought,” says Smith. “Most of our results have been big surprises that continue to astound us.”

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