A simple model for characterizaing innate immunity in the context of the intact organism

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New genome sequences are changing the way we think about animal immunity. Some invertebrate animals that were thought to have relatively simple immune systems now appear to have complex families of immune recognition proteins that operate differently from the well characterized systems in mammals and insects. The sea urchin genome sequence reveals this type of immune system and an understanding of how it works will provide new approaches to controlling microbes and fresh understanding of the origins and mechanisms of our own immune system. To bring this static genome sequence to life we need biologically relevant animal models. The sea urchin larva provides an attractive model for a number of reasons: (1) it is a simple organism of only a few thousand cells, (2) it is a feeding animal in which the interactions between the immune system and microbes in the gut can be efficiently characterized, (3) there are many tools available to manipulate gene expression in order to test networks of gene interactions and (4) it belongs to an animal group that is closely related to ourselves. We will identify key regulatory interactions that mediate gut immunity in this simple organism to build a model that describes how genes are turned on and off in the course of an antibacterial immune response. Because the larva is so small we can image its immune cells as the response takes place and use fluorescent reporter constructs to monitor activity of specific genes. We can then investigate how the system responds to pathogenic or symbiotic microbes. Ultimately we can apply what we find in this simple model system to more complex human biology.