Epigenetics of non-model organisms

在20世纪的大部分时间里，模式生物一直是研究的主要内容。在某种程度上，模式生物因其直接的发育和恒定的形态而被选择。然而，快速基因组测序的出现和分子工具随时转移到非传统模式生物已经模糊了模型，新兴和非传统模式生物之间的界限。非传统模式生物更复杂的生活史提供了一个独特的机会来扩展我们对生物学的理解。我提出的研究计划将探索非传统模式生物生物学的表观遗传学基础。例如，像老鼠和人类一样，果蝇在发育过程中对适度的营养剥夺的反应，没有什么比发育成更小的成年人更令人兴奋的了。相反，水蚤对不利环境的反应是产生额外的性别——雄性。同样，在有捕食者的情况下，水蚤的形态也会发生很大的改变，它们可以长出巨大的头盔、尾刺、棍棒、颈齿和其他形态上的精致，完全改变了它们的外观。这些旺盛的形态变化必然是表观遗传的，因为它们发生在具有相同基因组的克隆中。这些戏剧性的和生物学上必不可少的表观遗传反应表明了非传统模式生物的优势。表观基因组反映了基因表达的一系列表观遗传变化；也就是说，基因表达的变化不是由于DNA序列的改变。表观基因组响应外部环境因素，如营养、毒素暴露、激素环境、社会互动，甚至可能是天气。文献记载较少的是细胞内环境的影响，特别是内细菌的影响。在具有专性细胞内繁殖的内细菌中，a-变形细菌可以说是最著名的，因为这一群体的一个古老成员产生了我们的线粒体。然而，这种普遍存在的细菌群也包括较少驯化的现存亲戚，沃尔巴克氏体和立克次体，分别是无脊椎动物和脊椎动物的专性内细菌。我将通过探索它们在非传统模型系统、水蚤、蜱虫和哺乳动物细胞培养中对宿主基因组的控制来扩展我们在果蝇内细菌的表观遗传效应方面的工作。无处不在的内细菌控制宿主的多种方式，从而影响宿主的表型和生物学，是本研究计划将要解决的问题。

Model organisms have been the mainstay of research for much of the 20th century. In part, model organisms have been selected for their straightforward development and constant morphology. However, the advent of rapid genome sequencing and the ready transfer of molecular tools to non-traditional model organisms have blurred the lines between model, emerging and non-traditional model organisms. The more complex life histories of non-traditional model organisms provide a unique opportunity to expand our understanding of biology. My proposed research program will explore the epigenetic foundation of the biology of non-traditional model organisms. For example, Drosophila like mice and humans, responds to modest nutrient deprivation in development by nothing more exciting than developing as smaller adults. In contrast, Daphnia responds to adverse environmental circumstances by producing an additional sex - males. Similarly, in the presence of predators, the morphology of Daphnia is grossly remodeled and the animals can produce massive helmets, tail spines, clubs, neck teeth and other morphological elaborations that completely change their appearance. These exuberant morphological changes are necessarily epigenetic, as they occur in clones with identical genomes. These dramatic and biologically essential epigenetic responses demonstrates the advantages of non-traditional model organisms. The epigenome reflects the suite of epigenetic changes in gene expression; that is, changes in gene expression not due to altered DNA sequence. The epigenome is responsive to external environmental factors such as nutrition, toxin exposure, hormonal milieu, social interactions, and possibly even the weather. Less well documented is the effect of the internal environment of cells, in particular the effect of endobacteria. Among the endobacteria, bacteria with obligate intracellular reproduction, a-proteobacteria is arguably the most famous, as an ancient member of this group gave rise to our mitochondria. However, this ubiquitous group of bacteria also includes less domesticated extant relatives, Wolbachia and Rickettsia, obligate endobacteria of inverterbrates and vertebrates, respectively. I will extend our work on the epigenetic effects of endobacteria in Drosophila by exploring their control of their host's genome in the non-traditional model systems, Daphnia, ticks and mammalian cell culture. The manifold ways in which ubiquitous endobacteria control their host, and so influence host phenotype and biology, are the questions that will be tackled in this research programme.