Spatial and temporal regulation of macromolecular complex formation in bacteria

微生物学领域的最新发展揭示了细菌细胞复杂组织和不同细胞组分之间动态相互作用的新见解。这些意想不到的发现，彻底改变了多年来流行的细菌细胞作为“自由扩散的大分子袋”的观点，由于不同专业领域的结合和多学科方法的使用，这些发现成为可能。这五个合作的PI为这场革命做出了重大贡献。了解细菌细胞的时空和结构组织，它们背后的机制及其生理意义，这对基础科学和应用科学至关重要，需要汇集不同的学科和实验方法。本研究的目的是揭示细菌细胞内大分子复合物的空间分布及其内在机制，并探索亚细胞时空组织的生理作用。具体而言，我们建议阐明战略的空间调控细菌多因子信号复合物，研究调控的RNA定位介导的信号网络，并探讨时空动态的染色体包装及其表达。为了实现这些目标，我们将进行跨学科的研究，从而我们将联合收割机尖端和定量成像方法与遗传，生物化学和蛋白质组学方法相结合。为了实现我们的目标，迫切需要五个研究小组联合收割机的力量，把他们不同领域的专业知识用于合作研究。为了实现这一目标，并确保交叉受精，博士后和博士生将在彼此的实验室中度过更长的时间，五个小组的所有成员将每八个月开会一次，讨论结果并计划未来的实验。这种合作模式将允许分享知识和技术，将大大提高参与这项研究的年轻科学家-学生，博士后和PI-的知识和专业知识，并将保证项目的成功。拟议的合作研究对基础科学很重要，因为它们有望揭示微生物细胞生物学的新原理。此外，我们的研究有望开辟新的治疗途径，因为迄今未知的组织机制的组成部分将成为开发新抗菌药物的新的潜在靶点。

Latest developments in the field of microbiology revealed novel insights on the intricate organization of the bacterial cell and the dynamic interaction between the different cellular components. These unexpected revelations, which completely changed the view of bacterial cells as "bags of freely diffusing macromoleclules" that prevailed for many years, have been made possible due to the combination of different areas of expertise and the use of multidisciplinary approaches. The five collaborating PIs made significant contributions to this revolution. An understanding of the spatiotemporal and structural organization of the bacterial cell, the mechanisms underlying them and their physiological significance, which is of utmost importance for basic, as well as applied science, requires bringing together different disciplines and experimental approaches. The objectives of this proposal are to unravel the spatial distribution of macromolecular complexes in bacterial cells and its underlying mechanisms, as well as to explore the physiological roles of the subcellular spatiotemporal organization. Specifically, we propose to elucidate strategies for spatial regulation of bacterial multi-factorial signaling complexes, study regulation of signaling networks mediated by RNA localization, and explore the spatiotemporal dynamics of chromosome packaging and its expression. To achieve these goals we will pursue an interdisciplinary study, whereby we will combine cutting-edge and quantitative imaging methodologies with genetic, biochemical and proteomic approaches. To reach our goals, there is an urgent need for the five research groups to combine forces and bring their different areas of expertise to the collaborative studies. To achieve that and to ensure cross-fertilization, postdocs and PhD students will spend extended periods of time in each other labs, and all members of the five groups will meet every eight months to discuss the results and plan future experiments. This mode of cooperation will allow sharing knowledge and technologies, will greatly advance the knowledge and expertise of the young scientists - students, postdocs and PIs alike - who are involved in this research, and will guarantee the success of the projects. The proposed collaborative studies are important for basic science, as they are expected to uncover novel principles of microbial cell biology. Additionally, our research is expected to open up new therapeutic avenues, since components of the hitherto unknown organizational mechanisms will serve as novel potential targets for the development of new antibacterial drugs.