Strange Kevin
Departments of Anesthesiology, Molecular Physiology and Biophysics, and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
J Exp Biol. 2007 May;210(Pt 9):1622-31. doi: 10.1242/jeb.000125.
Molecular biology drove a powerful reductionist or ;molecule-centric' approach to biological research in the last half of the 20th century. Reductionism is the attempt to explain complex phenomena by defining the functional properties of the individual components that comprise multi-component systems. Systems biology has emerged in the post-genome era as the successor to reductionism. In my opinion, systems biology and physiology are synonymous. Both disciplines seek to understand multi-component processes or 'systems' and the underlying pathways of information flow from an organism's genes up through increasingly complex levels of organization. The physiologist and Nobel laureate August Krogh believed that there is an ideal organism in which almost every physiological problem could be studied most readily (the 'Krogh Principle'). If an investigator's goal were to define a physiological process from the level of genes to the whole animal, the optimal model organism for him/her to utilize would be one that is genetically and molecularly tractable. In other words, an organism in which forward and reverse genetic analyses could be carried out readily, rapidly and economically. Non-mammalian model organisms such as Escherichia coli, Saccharomyces, Caenorhabditis elegans, Drosophila, zebrafish and the plant Arabidopsis are cornerstones of systems biology research. The nematode C. elegans provides a particularly striking example of the experimental utility of non-mammalian model organisms. The aim of this paper is to illustrate how genetic, functional genomic, molecular and physiological methods can be combined in C. elegans to develop a systems biological understanding of fundamental physiological processes common to all animals. I present examples of the experimental tools available for the study of C. elegans and discuss how we have used them to gain new insights into osmotic stress signaling in animal cells.
分子生物学在20世纪后半叶推动了一种强大的还原论或“以分子为中心”的生物学研究方法。还原论试图通过定义构成多组分系统的各个组分的功能特性来解释复杂现象。系统生物学在后基因组时代作为还原论的继承者而出现。在我看来，系统生物学和生理学是同义词。这两个学科都试图理解多组分过程或“系统”以及从生物体基因到越来越复杂的组织层次的潜在信息流途径。生理学家兼诺贝尔奖获得者奥古斯特·克罗格认为，存在一种理想的生物体，几乎每一个生理问题都可以在其中最容易地进行研究（“克罗格原理”）。如果研究者的目标是从基因水平到整个动物来定义一个生理过程，那么对他/她来说最适合利用的模型生物体将是一种在遗传和分子方面易于处理的生物体。换句话说，一种能够方便、快速且经济地进行正向和反向遗传分析的生物体。非哺乳动物模型生物体，如大肠杆菌、酿酒酵母、秀丽隐杆线虫、果蝇、斑马鱼和植物拟南芥，是系统生物学研究的基石。线虫秀丽隐杆线虫为非哺乳动物模型生物体的实验效用提供了一个特别显著的例子。本文的目的是说明如何在秀丽隐杆线虫中结合遗传、功能基因组学、分子和生理学方法，以形成对所有动物共有的基本生理过程的系统生物学理解。我展示了可用于研究秀丽隐杆线虫的实验工具的例子，并讨论了我们如何利用它们来获得对动物细胞渗透应激信号传导的新见解。
