Identification and analysis of gene batteries in caenorhabditis elegans

基因的空间和时间表达受到精确的调控，以确保它们在发育和行为中发挥适当的结构和功能作用。基因调控的一个关键水平涉及将基因附近的一组小DNA片段与特定蛋白质结合。这样的小DNA片段被称为元件或基序，这样的蛋白质被称为转录因子。蛋白质复合体、信号转导通路和细胞器的许多分子成分之所以共表达，只是因为它们共享一组相似的这样的基序。这些共表达的基因构成了一个基因电池。我的研究计划旨在通过计算和实验相结合的方法检查每个基因的模体，从而定义基因电池。我选择圆虫线虫作为我的模式生物，是因为它易于维护和在实验室中使用；它在过去40年里得到了很好的研究；而且基本的生物学过程是保守的，所以从线虫身上获得的知识可以很容易地应用于包括人类在内的其他物种。预计该计划的结果将促进我们对新基因的调控和功能的理解，这些新基因基于它们与已知基因的关联(“关联而有罪”)，关于基因电池中基因之间的协调，以及基因电池之间的网络关系。基因电池的一个例子是X-box基因电池，之所以这样命名，是因为基因电池的所有成员在基因组中的邻近部分都携带一个X-box基序。虽然这些成员不一定具有共同的功能，但它们在一个共同的亚细胞室-纤毛中共同表达。因此，这些蛋白质的突变可能导致纤毛细胞的突变/疾病状态，表现为线虫的化学接收缺陷，以及人类的Bardet-Biedl综合征，在致命病例中，肥胖、视网膜色素病变、多指、智力低下、性腺功能低下和肾功能衰竭。该研究项目还将通过提供生物学和计算技能方面的接触和经验，为培训学生、博士后研究员和科学程序员提供一个独特的机会。

The spatial and temporal expression of genes is precisely regulated to ensure their appropriate structural and functional role in development and behavior. A critical level of gene regulation involves binding of a set of small DNA fragments in the neighborhood of a gene to specific proteins. Such small DNA fragments are called elements or motifs, and such proteins are called transcription factors. Many molecular components of protein complexes, signal transduction pathways, and cellular organelles are co-expressed simply because they share a similar set of such motifs. Such co-expressed genes constitute a gene battery. My research program is designed to define gene batteries by examining the motifs for each gene using combined computational and experimental approaches. I choose the round worm C. elegans as my model organism because it is easy to maintain and work with in the laboratory; it has been well studied over the past four decades; and fundamental biological processes are conserved, so knowledge gained in C. elegans can be readily applied to other species including humans. It is anticipated that the outcome of this program will promote our understanding about the regulation and function of novel genes based on their association with known genes ("guilty by association"), about the coordination among genes within a gene battery, and about the networking relationship among gene batteries. An example of a gene battery is the X-box gene battery, so named because all members of the gene battery carry an X-box motif in its neighborhood in the genome. Although these members do not necessarily share common functionality, they are co-expressed in a common subcellular compartment, the cilium. Consequently, mutations in these proteins may lead to a mutant/disease condition in ciliated cells, which manifests itself as a defect in chemoreception in C. elegans, and the Bardet-Biedl Syndrome in humans, a constellation of obesity, pigmentary retinopathy, polydactyly, mental retardation, hypogonadism, and renal failure in fatal cases. The research program will also provide a unique opportunity for training students, postdoctoral fellows and scientific programmers by offering a combined exposure and experience in biology and computational skills.