Establishing the hierarchies in regulation .... in time

人类、动物、植物，甚至是我们肉眼看不见的生物(如制造面包和啤酒的酵母)，都能非常好地适应环境的变化。后者包括温度、食物供应的变化，以及接触尼古丁和酒精等有毒化学物质。这种适应往往比对人造系统的适应好得多。因此，我们渴望从生物学中学习如何适应才能如此有效。有人可能会认为，现在这应该很容易了，因为“基于DNA测序的功能基因组学”提供了如此多的实验结果。然而，新结果的数量如此惊人，以至于很难只看到树木而看到森林。科学家们需要直截了当的方法来解释这些结果，就它们对适应和调节的含义而言。我们最近获得的证据表明，生物适应之所以如此有效，是因为它调用了一系列调控机制。最先发挥作用的机制可能是那些始终处于待机状态但效率较低的机制。随后被取消的方案最终可能会更有效，但成本太高，不能一直处于待机状态。我们在这里提出一个研究项目，它将建立一种精确的方法来从实验上证明这一点。我们将在这里开发的新方法被称为时间依赖规则分析。对于正在适应氮(或糖)短缺的酵母细胞来说，这一点将得到完全证明。我们希望了解生物学如何在微妙而有效的调控方面击败人工系统。这具有改善人造控制系统的前景，以及对环境友好的啤酒、面包和新生物制品的生产。

Humans, animals, plants and even living creatures so small that we can not see them with our naked eye (such as the yeasts that make our bread and beer), can adapt remarkably well to changes in their environment. The latter include changes in temperature, food supply, and exposure to toxic chemicals such as nicotin and alcohol. The adaptation is often much better than the adaptation of man-made systems. Hence we are eager to learn from Biology how the adaptation can be so effective. One might think that this should be easy now, with 'DNA-sequencing based functional genomics' delivering so many experimental results. However, the amounts of new results are so staggering that it is hard to see the forest for the trees. The scientists are in need of straightforward ways to interpret those results in terms of what they imply for adaptation and the regulation thereof. We recently obtained evidence suggesting that biological adaptation is so effective because it invokes a succession of regulatory mechanisms. The mechanisms that come into play first may be ones that are always on stand-bye but less efficient. The ones that are onvoked subsequently, may be more effective ultimately but are too 'expensive' to keep on stand-bye all the time. We here propose a research project that will establish a precise method to prove this experimentally. The new method that we shall develop here is called time-dependent regulation analysis. It will be demonstrated completely for yeast cells that are adapting to a shortage of nitrogen (or sugar). We expect to learn how Biology still beats man-made systems in terms of subtle and efficient regulation. This has the perspective of improving man-made control systems, as well as the environmentally friendly production of beer, bread and new biologicals.