Understanding cell division control and dynamics in Streptomyces and Mycobacteria

每个细胞都必须分裂才能生长和繁殖。在大多数细菌中，细胞的分裂是由一个大型的多组分分裂机器完成的。这台机器的核心是一种叫做FtsZ的蛋白质，它组装成一个支架，对募集额外的细胞分裂蛋白质至关重要。基础研究中的一个关键问题是了解细胞如何控制ftsz支架组装的正确时间和结构。此外，研究细胞分裂的过程是非常有趣的，因为它可以帮助设计新的抗生素，专门针对威胁健康的细菌的细胞分裂复合体的成分。我们最近发现了一种细胞分裂机制的新成分，它可以调节无害的抗生素产生细菌链霉菌中ftsz -支架组装的动力学。重要的是，这种新的支架调节因子也存在于许多严重的病原体中，如结核分枝杆菌或白喉。因此，获得链霉菌细胞分裂机制的基本理解将有助于我们更多地了解其致病亲属如何分裂，并可能为开发抑制这些微生物病原体细胞分裂的创新策略提供机会。由于完全不知道这种新的调节剂如何控制细菌中的细胞分裂，我们的目标是a)表征调节剂在链霉菌和分枝杆菌中的功能)确定调节剂如何在体外影响FtsZ支架组装的动力学)了解调节剂与FtsZ相互作用的结构基础为了实现这些目标，我们将采用一系列分子，细胞生物学和生化技术，并补充我们的功能表征研究与结构阐明调节本身和复杂的FtsZ。

Every cell must divide in order to grow and to propagate. In most bacteria, the splitting of the cell is accomplished by a large, multi-component division machine. At the heart of this machine is a protein called FtsZ, which assembles into a scaffold that is essential for the recruitment of additional cell division proteins. One of the key questions in fundamental research is to understand how cells control the correct timing for the assembly and the architecture of the FtsZ-scaffold. In addition, studying the process of cell division is of great interest because it can help with the design of new antibiotics that specifically target components of the cell division complex in health-threatening bacteria.We have recently identified a novel component of the cell division machinery that regulates the dynamics of the FtsZ-scaffold assembly in the harmless antibiotic producing bacteria Streptomyces. Importantly, this new scaffold regulator is also present in many serious pathogens like M. tuberculosis or C. diphtheriae. Consequently, gaining a fundamental understanding of the mechanism of cell division in Streptomyces will help us learn more about how their disease-causing relatives divide and may offer the opportunity to develop innovative strategies to inhibit cell division in these microbial pathogens.Since it is completely unknown how this new regulator controls cell division in bacteria, we aim to a) Characterise the function of the regulator in Streptomyces and Mycobacteriab) Determine how the regulator influences the dynamics of FtsZ scaffold assembly in vitroc) Understand the structural basis for the interaction of the regulator with FtsZTo achieve these aims, we will employ a range of molecular, cell biological and biochemical techniques and complement our functional characterisation studies with the structural elucidation of the regulator on its own and in complex with FtsZ.