GLOBAL CONTROL OF DIFFERENTIATION IN CAULOBACTER

一个细胞如何分化成不同的细胞类型是其中之一 生物学中的基本问题。细胞可以通过一种方式 分化是通过已经不对称的母细胞的细胞分裂来实现的。 这些不对称的细胞分裂在所有王国的生物体中都是常见的， 包括人类，果蝇，线虫线虫 线虫、酵母菌以及枯草芽孢杆菌和硫杆菌等细菌 新月星座。我们想要了解全球控制对 铜绿假单胞菌细胞分化过程中不对称性的产生 新月星座。在这个简单的有机体中，细胞分裂产生了两个 形态和功能不同的子代细胞：一种能动的 蜂群细胞和一种无柄柄细胞。这种差异是由于 不对称性在分裂前细胞中的表达 不同的极域。这根杆子将会产生沼泽细胞 只有一根鞭毛，另一根有柄。这种不对称性 反映许多内部过程，例如本地化 蛋白质，细胞类型特异性DNA复制，染色体的建立 结构，时间控制的DNA甲基化，和定位 抄写。因此，电极生物合成的研究提供了一种方便的 对这些机制的分析。硫杆菌作为一种细菌的一大优势 实验系统是细胞群体可以很容易地 在不干扰细胞正常生理的情况下进行同步。我们 将研究参与全球控制的三个基因的作用 铜绿假单胞菌的分化和细胞分裂如何决定时间 和位置信息进行整合，以获得适当的 差异化。RpoN，编码sigma-54转录的基因 因子是极体生物合成和细胞分裂的全球调节器， GDNA控制极性结构的定位，并参与 在细胞分裂过程中保持法向对称轴，以及FtsZ 是一种GTP结合蛋白，参与细胞分裂的启动和 秸秆的生物合成。这些基因控制着基因的表达和 细胞所需的多种基因和基因产物的定位 差异化。通过确定丰度和局部性如何 这些全球调控因子在细胞周期中受到控制，以及如何 它们相互作用，我们将解决细胞的基本机制 差异化。这将进一步加深我们对不对称性的了解 产生了一个问题，这个问题对于我们理解 原核生物和真核生物的生物系统。事实上，有一些 疾病，如癌症，是由于失去对 细胞分化。

How one cell differentiates to give rise to different cell types is one of the fundamental problems in biology. One way by which cell can differentiate is by cell division of an already asymmetric mother cell. These asymmetric cell divisions are common to organisms of all kingdoms, including humans, the fruit fly Drosophila, the nematode Caenorhabditis elegans, yeast, and bacteria such as Bacillus subtilis and Caulobacter crescentus. We want to understand the global controls responsible for the generation of asymmetry during cellular differentiation in Caulobacter crescentus. In this simple organism, cell division gives rise to two morphologically and functionally different progeny cells: a motile swarmer cell and a sessile stalked cell. This differentiation is due to the expression of asymmetry in a predivisional cell that has two different polar domains. The pole that will give rise to the swarmer cell has a single flagellum and the other one has a stalk. This asymmetry reflects numerous internal processes, such as the localization of proteins, cell type specific DNA replication, establishment of chromosome structure, temporally controlled DNA methylation, and localized transcription. Thus, the study of pole biosynthesis provides a convenient assay of these mechanisms. A major advantage of Caulobacter as an experimental system is the ease with which cell populations can be synchronized without perturbing the normal physiology of the cell. We will study the role of three genes involved in the global control of Caulobacter differentiation and cell division to determine how temporal and positional information are integrated in order to obtain proper differentiation. rpoN, the gene encoding the sigma-54 transcription factor, is a global regulator of pole biosynthesis and cell division, gdnA controls the positioning of polar structures and is involved in maintaining the normal axis of symmetry during cell division, and FtsZ is a GTP-binding protein involved in the initiation of cell division and of stalk biosynthesis. These genes control the expression and localization of a multitude of genes and gene products required for cell differentiation. By determining how the abundance and the localization of these global regulators is controlled during the cell cycle and how they interact, we will address the basic mechanisms of cell differentiation. This will further our knowledge of how asymmetry is generated, a question central to our understanding of the development of both prokaryotic and eukaryotis biological systems. Indeed, a number of diseases, like cancer, result from a loss of the proper control of cellular differentiation.