'Dissertation Research: Genetic Variation in Induction Kinetics and Antibacterial Strength of Drosophila Immunity Genes'

Clark&Amp；LazzaroInsects面临着一系列不同的病原体，它们通过全身免疫反应来对抗这些病原体。来自野生种群的果蝇品系在免疫反应方面存在广泛的遗传差异，品系之间感染后的死亡率和感染期间所承受的内部病原体负荷存在差异。果蝇免疫反应的一个重要组成部分是由抗菌肽提供的，抗菌肽是为应对败血症损伤而合成的。初步结果还显示，果蝇品系之间在一种抗菌肽的转录诱导性方面存在显著差异。虽然之前和正在进行的DNA序列变异调查已经在果蝇抗菌肽中发现了编码变异，但这些基因在感染后转录诱导的速度和强度的差异也可能是重要的。这项研究将彻底量化在自然种群中分离的黑腹果蝇免疫效力的表型变异量。感染后的死亡率，内部病原体生长的抑制，以及6个抗菌基因的转录诱导能力将在150个第二染色体替换系中进行检测。我们将探讨诱导动力学和免疫之间的关系。几个免疫系统基因将在这些品系的子集中被完全测序，并且所有品系的分子标记都将被评分。将测试抗菌基因启动子的核苷酸多态、这些基因的转录强度和整个生物体表型之间的统计关联。这项工作将第一次看到天然遗传变异在先天性免疫应答中的结构，并将解决自然选择如何驱动转录控制和先天性免疫进化的基本问题。

0073598Clark & LazzaroInsects face a diverse array of pathogens, which they combat with a generalized immune response. There is extensive genetic variation in immune responsiveness among Drosophila lines derived from a wild population, with differences between lines in mortality rate following infection and in internal pathogen load sustained during infection. A substantial component of the Drosophila immune response is provided by antibacterial peptides which are synthesized in response to septic injury. Preliminary results also show significant variation among Drosophila lines in the transcriptional inducibility of one antibacterial peptide. While previous and ongoing surveys of DNA sequence variation have uncovered coding variants in Drosophila antibacterial peptides, variation in the speed and strength of transcriptional induction of these genes following an infection may also be important. This study will thoroughly quantify the amount of phenotypic variation in immune efficacy segregating in a natural population of Drosophila melanogaster. Mortality rate following infection, suppression of internal pathogen growth, and the transcriptional inducibility of six antibacterial genes will be examined in 150 2nd-chromosome replacement lines of D. melanogaster. Correlations between induction kinetics and immunity will be explored. Several immune system genes will be completely sequenced in a subset of these lines, and molecular markers will be scored in all lines. Statistical associations between nucleotide polymorphisms in antibacterial gene promoters, the transcriptional intensity of those genes, and whole organism phenotypes will be tested. This work will provide a first look at the structure of natural genetic variation in innate immune responsiveness, and will address fundamental question of how natural selection drives the evolution of transcriptional control and innate immunity.