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，现在似乎拥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具有良好特征的系统不同。海胆基因组序列揭示了这种免疫系统，了解它的工作原理将为控制微生物提供新的方法，并对我们自己的免疫系统的起源和机制有新的理解。为了让这个静态的基因组序列重现生机，我们需要具有生物学意义的动物模型。海胆幼虫提供了一个有吸引力的模型，原因如下：(1)它是一个只有几千个细胞的简单生物体；(2)它是一种食性动物，可以有效地描述免疫系统和肠道微生物之间的相互作用；(3)有许多工具可以操纵基因表达，以测试基因相互作用网络；(4)它属于与我们密切相关的动物群体。我们将确定在这个简单的有机体中调节肠道免疫的关键调控相互作用，以建立一个描述基因在抗菌免疫反应过程中如何打开和关闭的模型。由于幼虫如此之小，我们可以在反应发生时对其免疫细胞进行成像，并使用荧光报告结构来监测特定基因的活动。然后我们可以研究系统对致病微生物或共生微生物的反应。最终，我们可以将我们在这个简单的模型系统中发现的东西应用到更复杂的人类生物学中。

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.