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

新的基因组序列正在改变我们对动物免疫力的看法。 一些被认为具有相对简单的免疫系统的无脊椎动物现在似乎具有复杂的免疫识别蛋白家族，其运作方式与哺乳动物和昆虫中的良好表征系统不同。 海胆基因组序列揭示了这种类型的免疫系统，了解它是如何工作的将提供新的方法来控制微生物和新的理解我们自己的免疫系统的起源和机制。 为了让这个静态的基因组序列变得有生命，我们需要生物学上相关的动物模型。 海胆幼虫提供了一个有吸引力的模型，原因有很多：（1）它是一种只有几千个细胞的简单生物体，（2）它是一种摄食动物，其中免疫系统和肠道中微生物之间的相互作用可以有效地表征，（3）有许多工具可用于操纵基因表达，以测试基因相互作用的网络，以及（4）它属于一个与我们密切相关的动物群体。 我们将确定在这个简单的生物体中介导肠道免疫的关键调控相互作用，以建立一个模型，描述基因在抗菌免疫反应过程中如何打开和关闭。 因为幼虫是如此之小，我们可以成像其免疫细胞的反应发生，并使用荧光报告构建监测特定基因的活动。 然后，我们可以研究该系统如何对致病或共生微生物作出反应。 最终，我们可以将我们在这个简单的模型系统中发现的应用于更复杂的人类生物学。

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.