SUNNYBROOK HEALTH SCIENCES CENTRE

SUNNYBROOK HEALTH SCIENCES CENTRE

November 09, 2006 15:37 ET

Study of sea urchin reveals insight into human immune system

Genome sequence reveals complex immune system with important implications for more research and treatment for human illness

Attention: Environment Editor, Health/Medical Editor, Lifestyle Editor, Science Editor TORONTO/ONTARIO--(CCNMatthews - Nov. 9, 2006) - A look at the genome sequence of the purple sea urchin by scientists at Sunnybrook Research Institute has uncovered an unexpectedly elaborate immune system with both important similarities and revealing differences to that of humans.

These findings reinforce the value of the sea urchin model for investigations aimed at understanding human immunity and as a source of novel immune mechanisms that can be directed towards developing antibiotic treatments.

The research, to be published in the November 10 issue of Science, indicates that a much broader understanding of our own immune system is possible through the study of the sea urchin (Strongylocentrotus purpuratus), which is more closely related to vertebrates such as humans than are standard invertebrate models like the fruit fly. Simple invertebrate animals such as the sea urchin larva provide powerful models with which to unravel the complex gene networks that regulate immunity.

The study was led by Jonathan Rast, a scientist in Molecular and Cellular Biology at Sunnybrook Research Institute, and assistant professor, Medical Biophysics, University of Toronto in conjunction with other researchers from around the world who are interested in animal immunity. The work was part of a community-wide effort to characterize the sea urchin genome organized by the Baylor College of Medicine Human Genome Sequencing Center and the California Institute of Technology.

The work is an overview of what the genome sequence conveys about immunity in the sea urchin and by inference, immunity in our invertebrate and vertebrate ancestors. Findings provide a new perspective of invertebrate immunity and of the evolutionary origins of the human immune system. Surprising findings include counterparts of genes involved in human adaptive immunity (the type of immunity that allows us to produce antibodies) that were previously unknown outside of vertebrates. The findings from the genome reveal an enormous complexity of innate immune receptors (i.e., microbial recognition proteins that are hardwired in the genome) that are represented by comparatively modest gene families in other animals.

Sea urchins are members of the echinoderm phylum, an animal group which also includes sea stars and is closely allied with vertebrates. "With this study we are turning a corner in understanding immunity outside of vertebrates. It provides an unprecedented complexity of immune receptors for in-depth study and illuminates the evolutionary origins of our immune system," says Rast, who is also the winner of an Early Researcher Award (ERA) from the Ontario Ministry of Research and Innovation.

"Genomics has completely revolutionized the ability to look at immunity in invertebrates," says Rast. "Genome sequences greatly increase the sensitivity of detecting important immune genes over traditional molecular gene hunting technologies. For the sea urchin and other invertebrates this means that after decades of inefficient searching, we suddenly have our hands on a goldmine of information."

Importantly, although the adult sea urchin is a complex animal, the embryo and larva of the sea urchin provide a very simple model to study how genes interact. The genome allows this approach to be applied to questions of immunity. "The long-term goal is a deep understanding of the operation of a simple immune system with relevance to our own," says Rast. "It will enable us to understand immune cells in their normal state and then see why they become abnormal in cases such as leukemia and immune dysfunction."

Collaborators on the study include L. Courtney Smith from the Department of Biological Sciences of George Washington University, Gary W. Litman from the Department of Pediatrics, University of South Florida (USF) College of Medicine, and Mariano Loza-Coll and Taku Hibiono from Sunnybrook Research Institute.

Funding for this project in the Rast lab was provided by operating grants from the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC). Infrastructure funding was provided by the Canada Foundation for Innovation and Ontario Innovation Trust.

/For further information: www.sunnybrook.ca/ IN: HEALTH

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