Metabolomic systems biology analysis of differentiation in trypanosomes

系统生物学是一个术语，用于描述旨在通过重建组成给定系统的组成元素来理解生物功能的工作。在细胞这一构成所有生物体的基本单位的水平上，这种方法已经变得可行，因为识别给定细胞类型中的所有基因，跟踪这些基因是如何打开的，并测量由基因编码的蛋白质已经变得司空见惯。也可以测量维持细胞存活状态的小化学物质。后一种类型的测量已被证明比鉴定基因和蛋白质更困难，因为这些所谓的代谢物的化学复杂性。然而，技术进步现在已经能够对这些小化学物质进行全面采样，在许多方面，这些化学物质是生命的实际本质（基因代表产生构建细胞硬件的蛋白质的蓝图/而在系统内流动的代谢物代表细胞活力）。我们开创了技术进步，能够同时测量给定细胞内的数千种代谢物。在这里，我们计划使用这种技术来确定单细胞生物体非洲锥虫的代谢物如何变化，因为它在哺乳动物血流环境和患者之间携带这些寄生虫的采采蝇载体环境之间交替。系统生物学方法的核心将是开发计算机软件，这些软件将能够重建相互连接的大型代谢物网络以及其他网络，这些网络显示当锥虫在不同环境之间移动时相关代谢物的浓度如何变化。除了这些巨大的网络，我们还将开发方法，使我们能够识别在分化过程中发生变化的网络部分。然后，我们将专注于网络的选定部分，以确定影响细胞分化过程的特定代谢物如何流经该系统并影响细胞功能。

Systems biology is a term that has been coined to describe work that aims to understand biological function through the reconstruction of the component elements that comprise a given system. At the level of the cell, a basic unit from which all living organisms are made, this approach has become feasible since it has become commonplace to identify all of the genes in a given cell type, follow how those genes are turned on and to measure the proteins encoded by the genes. It is also possible to measure the small chemicals that maintain the cell in its viable state. This latter type of measurement has proven more difficult than identification of genes and proteins, because of the chemical complexity of these so-called metabolites. However, technological advances have now enabled comprehensive sampling of these small chemicals, which are, in many regards the actual essence of life (the genes representing a blue print that produces the proteins that build the cellular hardware / while the metabolites that flow within the system represent cellular vitality). We have pioneered technological advances that enable the measurement of thousands of metabolites simultaneously within a given cell. Here we plan to use this technology to identify how metabolites change in a single celled organism, the African trypanosome, as it alternates between the environment of the mammalian bloodstream and that of the tsetse fly vector that carries these parasites between patients. Central to the systems biology approach will be the development of computer software that will enable the reconstruction of large networks of metabolites that are connected to one another and other networks that show how related metabolites change in concentration as the trypanosome moves between the different environments. In addition to these huge networks, we will also develop methods that enable us to identify those parts of the network that change during the differentiation process. We will then focus on selected parts of the network to establish how particular metabolites, that influence the cellular differentiation process, flow through this system and impact on cellular function.