Molecular basis of stress and immune responses in teleost fish

不同种类的鱼对病原体有不同的反应。例如，大西洋鲑鱼对引起传染性鲑鱼贫血(ISA)的病毒病原体很敏感，而其他鲑鱼类，如虹鱼、褐鲑鱼和北极鲑鱼，对ISA具有抵抗力。人们还知道，不同种类的鱼对环境压力的反应可能不同，例如环境温度升高。鱼类免疫和应激反应的物种特异性差异所涉及的基因和生化途径知之甚少。我的研究项目将利用基因组学的力量来揭示与鱼类抵御病原体和环境压力有关的关键基因。这项工作使用了DNA微阵列(基因芯片)等基因组学工具，使研究人员能够同时研究数千个已知基因的表达。此外，由于目前可用的FISH微阵列缺少许多基因，我将创建新的基因组资源(消减cDNA文库)来鉴定未知的防御反应基因。我的方法是新颖的，因为它使用了三个进化上不同的鱼类群体(鲑鱼、大西洋鳕鱼和斑马鱼)对免疫原性刺激或环境压力的平行暴露，然后使用DNA微阵列、消减文库和其他基因组技术进行基因表达研究。此外，还将分析这些鱼类群体在胚胎发育过程中热应激的影响。生物信息学方法将用于比较不同物种对特定应激源的全球基因表达反应，并确定免疫或应激反应基因所代表的分子途径。对全球基因表达结果的跨物种比较将确定一些属于所有鱼类防御系统的基因，以及其他发挥谱系特异性防御反应的基因。这项研究将显著提高我们对鱼类如何保护自己免受病原体和环境胁迫的理解，并将对包括比较免疫学、进化生物学和水产养殖在内的几个研究领域具有价值。

Different fish species have characteristic responses to pathogens. For example, Atlantic salmon are susceptible to the viral pathogen causing Infectious Salmon Anaemia (ISA), while other salmonids such as rainbow trout, brown trout, and Arctic char, are resistant to ISA. It is also known that different fish species may respond differently to environmental stress such as increased ambient temperature. The genes and biochemical pathways involved in species-specific differences in fish immune and stress responses are poorly understood. My research program will use the power of genomics to reveal the key genes involved in fish defense against pathogens and environmental stress. This work uses genomic tools such as DNA microarrays (gene chips), which allow the researcher to study the expression of thousands of known genes simultaneously. In addition, because currently available fish microarrays are missing many genes, I will create new genomic resources (subtracted cDNA libraries) for identifying unknown defense response genes. My approach is novel in that it uses parallel exposures of three evolutionarily divergent groups of fish (salmonids, Atlantic cod, and zebrafish) to immunogenic stimuli or environmental stress, followed by gene expression studies with DNA microarrays, subtracted libraries, and other genomic techniques. In addition, the impact of thermal stress during embryonic development will be analyzed for these fish groups. Bioinformatic methods will be used to compare different species' global gene expression responses to a particular stressor, and to identify the molecular pathways represented by immune- or stress-responsive genes. Cross-species comparisons of global gene expression results will identify some genes that are part of all fish defense systems, and other genes that act in lineage-specific defense responses. This research will significantly improve our understanding of how fish protect themselves against pathogens and environmental stress, and will be valuable to several research areas including comparative immunology, evolutionary biology, and aquaculture.