Coordination Funds

质子动力(PMF)是能量新陈代谢的核心，为大多数细胞功能提供燃料。它作为遗传密码是普遍存在的，并一直在塑造着进化。PMF是一种跨膜的电化学梯度，通常由多个膜蛋白复合体的协同活动产生。它将能量转换从分子特性和化学计量限制中分离出来，并自由地连接和整合原本无关的细胞过程。这一功能一直是PMF成功的关键。在特别灵活的同时，PMF还必须严格可靠地为生化反应提供燃料并维护电池。为了保证能量供应，必须将环境和生理刺激整合到PMF调节中。尽管人们对PMF进行了深入研究，但人们对监管策略的理解仍然不够。最近，功能成像和生物传感技术揭示了线粒体PMF的新的基本特征。虽然这些洞察力已经开始改变我们对生物能量动力学的理解范式，但对于产氧光合作用，类似的洞察力还缺乏。然而，在光合作用的背景下研究PMF特别适合于作为一种方法来理解PMF动力学的基础原理，因为它特别容易由于自然生境中波动的光而发生快速的外部变化。这个研究小组(GoPMF)将开发如何调节PMF的产生和调制，以在多变的自然环境中优化光合作用输出的概念。在这一倡议成员最近的发现和方法发展的推动下，我们将在亚细胞组织和生理学的背景下评估光合作用生物能量学。我们将利用蓝藻和叶绿体作为体内模型，在翻译后和生理水平上剖析PMF快速调节的机制。这些见解将与对产生和调节PMF的分子机器的机械和结构分析联系在一起。将最先进的成像技术与原位生物传感技术的发展相结合，以监测活在单个细胞、细胞器和类囊体内的PMF的生物能量特征，将把我们对PMF管理的理解带入一个新的细胞生物学背景。通过快速时间分辨光谱、质谱学和结构生物学(包括低温EM和低温ET)，将获得驱动PMF动力学的机理的分子细节。广泛的基因工程将利用蓝藻、藻类和植物对PMF调节的机械保守性和多样性。这些功能研究的侧翼将是PMF的数学模型。我们期望建立对PMF的理解，将其理解为一个动态、响应和集成的中枢，它塑造了光合作用及其对外部快速变化的调节。

The proton motive force (PMF) is at the heart of energy metabolism and fuels most cellular functions. It is universal as the genetic code and has been shaping evolution. The PMF is an electrochemical gradient across a membrane, usually generated by the concerted activity of multiple membrane protein complexes. It separates energy transformation from molecular identities and stochiometric constraints and freely connects and integrates otherwise unrelated cellular processes. This feature has been key for the success of the PMF. While being particularly flexible, the PMF must also be strictly reliable to fuel biochemical reactions and to maintain the cell. To guarantee energy supply, environmental and physiological stimuli must be integrated into PMF regulation. Even though the PMF has been studied intensely, regulatory strategies remain insufficiently understood. Recently, functional imaging and biosensing techniques have uncovered novel, fundamental features of the mitochondrial PMF. While those insights have started to shift the paradigms of our understanding of bioenergetic dynamics, similar insights are lacking for oxygenic photosynthesis. Yet, studying PMF in the context of photosynthesis is particularly well suited as an approach to understand the principles underpinning PMF dynamics, because it is particularly prone to rapid external changes due to fluctuating light in natural habitats. This Research Group (GoPMF) will develop concepts of how the generation and modulation of the PMF is regulated to optimize photosynthetic output in changeable natural environments. Driven by recent discoveries and enabling methodological developments by members of this initiative, we will assess photosynthetic bioenergetics within its context of subcellular organization and physiology. We will make use of cyanobacteria and chloroplasts as in vivo models to dissect mechanisms of rapid PMF adjustment at the posttranslational and physiological level. These insights will be linked with mechanistic and structural analyses of the molecular machines that generate and modulate the PMF. Combining state-of-the-art imaging techniques, with the development of in situ biosensing techniques to monitor bioenergetic characteristics of the PMF live in individual cells, organelles and thylakoids will take our understanding of PMF management into a novel cell biological context. Mechanistic molecular detail into the mechanisms driving PMF dynamics will be gained through fast time-resolved spectroscopy, mass spectrometry and structural biology including cryo-EM and cryo-ET. Extensive genetic engineering will take advantage of the mechanistic conservation and diversity in PMF regulation by cyanobacteria, algae and plants. These functional studies will be flanked by mathematical modeling of the PMF. We expect to establish an understanding of the PMF as a dynamic, responsive and integrated hub that shapes photosynthesis and its adjustment to rapid external changes.