GLOBAL CONTROL OF DIFFERENTIATION IN CAULOBACTER

一个细胞如何分化产生不同的细胞类型是一个 生物学的基本问题。一种细胞可以 分化是通过已经不对称的母细胞的细胞分裂。 这些不对称的细胞分裂是所有界的生物体所共有的， 包括人类，果蝇，线虫，小杆线虫 线虫、酵母和细菌如枯草芽孢杆菌和柄杆菌 crescentus。我们想了解全球控制， 柄杆菌属细胞分化过程中不对称性的产生 crescentus。在这个简单的生物体中，细胞分裂产生两个 形态和功能不同的子代细胞：一种运动细胞， 一种为无柄细胞。这种差异是由于 在分裂前细胞中， 不同的极性域。会产生蜂群细胞的极点 只有一根鞭毛另一根有柄这种不对称性 反映了许多内部过程，例如 蛋白质，细胞类型特异性DNA复制，染色体建立 结构，时间控制的DNA甲基化， 转录。因此，对极生物合成的研究提供了一个方便的 分析这些机制。柄杆菌属作为一种 实验系统是容易与细胞群可以 同步而不干扰细胞的正常生理。我们 将研究三个基因在全球控制中的作用， 柄杆菌分化和细胞分裂，以确定如何时间 和位置信息进行整合，以便获得适当的 分化rpoN，编码sigma-54转录的基因 因子，是极生物合成和细胞分裂的全局调节因子， gdnA控制极性结构的定位，并参与 在细胞分裂过程中保持正常的对称轴，和FtsZ 是一种参与细胞分裂起始的GTP结合蛋白， 茎的生物合成。这些基因控制表达， 细胞生长所需的大量基因和基因产物的定位 分化通过确定它们的丰度和位置 在细胞周期中，这些全球调节因子的作用是如何被控制的， 它们相互作用，我们将解决细胞的基本机制， 分化这将进一步加深我们对不对称性 这是一个核心问题，我们对发展的理解。 原核生物和真核生物系统。事实上， 疾病，如癌症，是由于失去了适当的控制， 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.