SysMo: Ion and solute homeostasis in enteric bacteria: an integrated view generated from the interface of modelling and biological experimentation.

细菌细胞的生长和存活取决于它们维持相对恒定的细胞质的能力，在细胞质中发生产生蛋白质的生化过程。细胞质中必须保持相对恒定的主要元素是离子组成，简单离子，如钾、钠、氯、镁、铁和质子（pH）。一般来说，高钾浓度、低钠、氯和质子浓度对于产生生长和存活所需分子的酶的正常功能是理想的。镁和铁的细胞质库通过复杂的调控网络保持恒定，在本项目中不会直接考虑。当细胞不能将其细胞质维持在所需状态时，就会发生生长抑制，最终导致细菌死亡。这一观察结果有两个直接后果。首先，许多用于生产抗生素和新型治疗性蛋白质的大规模商业过程依赖于细菌生长-了解如何实现最佳生长是制药行业的主要目标之一。其次，细菌在体内的生长通常由免疫系统阻止，这可以通过使用抗生素来帮助。在食品加工和环境中，细菌的生长应该通过试图干扰细胞质的组成来限制。从这里提出的研究中产生的新见解将帮助我们了解如何优化对细菌细胞的抑制和杀灭。该项目建立在合作实验室的工作基础上，这些实验室试图了解调节细菌钾积累的机制，控制细胞质pH值和适应高盐条件。所有的合作伙伴都在他们的生物学研究中取得了卓越的成就，在这个项目中，他们现在加入了化学家，数学家，计算机科学家和物理学家，他们将建立预测细胞行为的模型。建模可以描述我们目前对生物过程的理解，如果模型的准确性很高，这取决于物理科学家和生物学家之间的明确沟通，模型将预测尚未进行的实验的结果。然后，研究人员可以设计实验来测试模型，然后允许模型得到改进。这一策略的最终成功在于能够准确预测特定实验的结果和细菌对环境中特定变化的反应。然后，这些信息可以用来尝试通知协议，无论是改善或减少细菌的生长和存活。

The growth and survival of bacterial cells is dependent upon their ability to maintain a relatively constant cytoplasm where the biochemical processes of producing proteins takes place. The major elements of the cytoplasm that must be maintained relatively constant are the ionic composition, simple ions, such as potassium, sodium, chloride, magnesium, iron and protons (pH). In general, a high potassium concentration, low sodium, chloride and proton concentrations are desirable for the normal functioning of enzymes that generate the molecules needed for growth and survival. The cytoplasmic pools of magnesium and iron are maintained constant by complex regulatory networks that will not be considered directly in the current project. When the cell cannot maintain its cytoplasm in the desired state, inhibition of growth occurs and, eventually, bacterial death results. This observation has two immediate consequences. Firstly, many large scale commercial processes for the production of antibiotics and novel therapeutic proteins rely on bacterial growth - understanding how to achieve the best growth is one the major objectives for the pharmaceutical industry. Secondly, the growth of bacteria in the body is normally prevented by the immune system, which can be aided by the use of antibiotics. In food processing and in the environment, bacterial growth should is limited by trying to interfere with the composition of the cytoplasm. New insights arising from the studies proposed here will help us to understand how we can optimise the inhibition and killing of bacterial cells. The project builds upon work in the partner laboratories that have sought to develop an understanding of the mechanisms that regulate potassium accumulation by bacteria, the control over the cytoplasmic pH and the adaptation to high salt conditions. All the partners have achieved excellence in their biological research and in this programme they are now joined by chemists, mathematicians, computer scientists and physicists who will to build models that predict the behaviour of cells. Modelling can describe our current understanding of a biological process and if the accuracy of the model is high, which is dependent on clear communication between the physical scientists and the biologists, the model will predict the outcome of experiments that have not yet been performed. The researchers can then design experiments that test the model and then allow the model to be refined. Ultimate success in this strategy is defioned by being able to predict accurately the outcome of specific experiments and the bacterial response to specific changes in the environment. This information can then be used to try to inform protocols that either improve or reduce bacterial growth and survival.