An evolutionary perspective in innate immunity using the nematode Caenorhabditis elegans

能够进行全面实验分析的简单模式生物在阐明复杂特征的分子遗传结构方面显示出巨大的潜力，从而增强了我们对包括人类在内的其他生物中这些特征的理解。在拟议的项目中，我们将利用线虫的优势作为实验系统来研究天然免疫的分子遗传学基础。特别是，我们将检查两个天然线虫菌株对革兰氏阳性细菌苏云金芽孢杆菌的诱导免疫反应。微阵列技术与Northern分析相结合，用于首次鉴定诱导基因表达。随后，通过对可用突变菌株的分析和使用RNA干扰的基因沉默来研究候选基因的确切功能。我们预计，这种方法将产生关于线虫免疫反应的保守和可变成分的信息。考虑到目前对包括线虫在内的低级无脊椎动物只有很少的信息，这些结果应该会为动物先天免疫系统的进化和功能提供新的见解。

Simple model organisms that are amenable to comprehensive experimental analysis show enormous potential to elucidate the molecular genetic architecture of complex traits and thus to enhance our understanding of these traits in other organisms, including humans. In the proposed project, we will exploit the advantages of the nematode Caenorhabditis elegans as an experimental system to study the molecular genetic basis of innate immunity. In particular, we will examine the induced immune response of two natural C. elegans strains towards the Gram-positive bacterium Bacillus thuringiensis. The microarray technology is employed in conjunction with Northern analysis for a first identification of induced gene expression. The exact function of candidate genes is subsequently studied by analysis of available mutant strains and by gene silencing using RNA interference. We expect that this approach will yield information about the conserved and variable components of the nematode's immune response. Considering that only little information is as yet available for lower invertebrates, including C. elegans, these results should provide novel insights into the evolution and function of the animal innate immune system.