Multitasking anti-pathogen activities of the sea urchin SpTransformer protein family: insights into an evolutionarily divergent metazoan immune system

George Washington University, Washington DC

Investigators

Abstract

Sea water has lots of marine bacteria. So, how do animals (sea urchins) that live in sea water protect themselves against infections? Answers to this question apply to successful management of marine populations and productive aquaculture. The sea urchin immune system lacks important aspects that are present in humans. For example, sea urchins do not produce antibodies. Instead, they express a family of anti-pathogen proteins called Transformer proteins (they change shape!). At least one of the Transformer proteins acts very broadly, and can bind to bacteria, fungi, and other pathogens. This is very different from one antibody that binds only one target. The hypothesis is that each Transformer protein has a slightly different repertoire of targets, which gives sea urchins great flexibility to protect themselves against pathogens with similar, different, or overlapping targets. Because of the large variety of slightly different Transformer proteins, their complex anti-pathogen activities are likely essential for sea urchins to survive. This project integrates research with education in the following manner. Artistic illustrations of science are effective for communicating science to the general public. An Introductory Biology course will be designed and taught specifically for fine arts majors by faculty in Biology and the Arts. Artist/scientist collaborations can improve whether people learn and understand important concepts in science, which will aid in science literacy. Furthermore, improved science understanding by environmental policy students could have impacts on official government policy. Sea urchins have a complex and robust anti-pathogen innate immune system comprised, in part, of SpTransformer (SpTrf; formerly Sp185/333) proteins. The recombinant (r)SpTrf-E1 protein binds to Vibrio and yeast but not to Bacillus. It binds LPS, beta-1,3-glucan, and flagellin, but not peptidoglycan. rSpTrf-E1 is intrinsically disordered and transforms to alpha-helical in the presence of anionic targets such as PO4 groups. The investigators predict that other versions of SpTrf proteins act similarly but recognize different but overlapping targets. They will attempt to define the binding sites for rSpTrf-E1, define the targets bound by other rSpTrf proteins, determine whether other rSpTrf proteins undergo conformational transformation like (r)SpTrf-E1, and test the anti-pathogen activities of other SpTrf proteins in vitro and in vivo. Outcomes are expected to clarify the binding and structural characteristics of the SpTrf proteins and their activities in host defense, providing a unique example of immunological adaptations by a basal deuterostome. Art to illustrate science is an effective way for communicating science to the general public. However, art students generally do not learn much in standard introductory science courses. Hence, an Introductory Biology course will be designed and taught specifically for fine arts majors by faculty in Biology and the Arts. The art inspiration will be the science learned from lectures, discussions, and contact with scientists. Outcomes will highlight opportunities for artist/scientist collaborations such as improved data illustration, and for environmental science policy students to learn about important concepts in science, which may have impacts on official government policy. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.