Understanding the decoding of calcium signals by calcium dependent enzymes and channels in plants - integrating experimental data and computational modeling

钙信号在动物、植物、真菌和微生物中的许多不同类型的细胞中都存在，并将信息从激动剂与细胞膜上的受体结合到细胞内部的靶点。所携带的信息具有令人惊叹的各种不同目的。因此，在植物中，许多内在的发育过程，以及对环境因素的即时反应都是由钙介导的。这一众多功能是如何由一个和相同的第二信使传达的，目前仍只有部分了解。这在植物生理学中尤其如此。首先，我们希望通过与Kudla、Grill、Hedrich和Romeis等人的合作，利用实验测定的刺参中钙依赖酶和钙通道的动力学来建立这些酶和通道的详细动力学模型。然后将这些模型与合作伙伴在植物细胞中测量的钙瞬变的实际实验数据相结合。因此，在没有详细的植物细胞钙信号转导机制模型的情况下，将有可能详细研究钙依赖蛋白对钙瞬变的信号解码。我们的第二个目标是建立一个植物细胞中钙信号的实际计算模型。与现有的工作相比，基于我们在这个项目中的工作，这个模型应该是生化机械的，在现有知识的最大可能程度上是定量的，但也应该足够灵活，以允许在后续项目中调整组织和生物的特定条件。我们意识到这实际上是一个挑战，因为只有很少的植物中钙信号转导的参与者被详细描述，其他的可能到目前为止还不知道。然而，即使是早期关于脊椎动物钙信号的研究也缺乏许多分子细节，由于能够进行虚拟实验和整合现有知识来探索某些假说并理解系统的定性和定量性质，因此对钙研究的进展是有利的。因此，由于模型无法拟合暗示给其他参与者的实际数据，因此发现了重要的机制。我们预计在这个项目中也会出现这种情况。我们将重点放在ABA和根中的盐(NaCl)反应以及保卫细胞中的ABA反应的背景下的钙信号，因为这些系统在研究组内进行了非常详细的研究，并且将有独特的数据收集作为我们模型的基础。

Calcium signalling occurs in many different cell types in animals, plants, fungi and microorganisms and carries information from agonists bound to receptors at the cell membrane to targets in the interior of the cell. The information carried serves an amazing variety of different purposes. Thus, in plants, many intrinsic developmental processes, but also immediate responses to environmental factors are mediated by calcium. How this multitude of functionalities is conveyed by one and the same second messenger is still only partially understood. This is especially true in plant physiology. We would like to increase the understanding of the information processing by following two objectives.First of all, in collaboration with the groups of Kudla, Grill, Hedrich and Romeis, we would like to make use of the experimentally determined kinetics of calcium dependent enzymes and channels in A. thaliana to build up detailed kinetic models of these. These models are then coupled to actual experimental data of calcium transients measured by the partners in plant cells. Thus, without having a detailed mechanistic model of calcium signal transduction in plant cells, it will be possible to study the signal decoding of calcium transients by calcium dependent proteins in detail. Our second goal is to build up an actual computational model of calcium signalling in plant cells. Compared to existing work and based on our work within this project, this model should be biochemically mechanistic and quantitative to the most possible degree with the current knowledge, but should be also flexible enough to allow adjustment to tissue and organism specific conditions in subsequent project. We are aware that this is actually a challenge due to the fact that only few of the players of calcium signalling in plants have been characterized in detail and others might not even be known so far. However, even early studies on calcium signalling in vertebrates which also lacked a lot of molecular detail, have been beneficial for the progress of calcium research due to the ability to conduct virtual experiments and integrate current knowledge to probe certain hypothesis and to understand the qualitative, as well as quantitative nature of the system. Thus, important mechanisms have been discovered due to the inability of models to fit the actual data hinting to additional players. We expect that this will be also the case in this project. We will focus on calcium signalling in the context of ABA and salt (NaCl) responses in root as well as ABA responses in guard cells, since these are the systems which are studied in great detail within the research group and for which a unique collection of data will be available as a basis for our models.