Understanding cell division control and dynamics in Streptomyces and Mycobacteria

了解链霉菌和分枝杆菌的细胞分裂控制和动力学

• 批准号: BB/T015349/1
• 负责人: Susan Schlimpert
• 金额: $ 63.56万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT015349%2F1
• 关键词: Understanding; cell; division; control; dynamics

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.

每一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名为FtsZ的蛋白质，它组装成一个支架，对于招募额外的细胞分裂蛋白质至关重要。基础研究的关键问题之一是了解细胞如何控制FtsZ支架组装和结构的正确时机。此外，研究细胞分裂过程是非常有趣的，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中的细胞分裂复合物的成分。我们最近已经确定了一种新的细胞分裂机制的组成部分，它调节无害的抗生素生产细菌链霉菌中FtsZ-支架组装的动力学。重要的是，这种新的支架调节剂也存在于许多严重的病原体中，如M。结核或C.白喉因此，对链霉菌细胞分裂机制的基本了解将有助于我们更多地了解其致病亲戚是如何分裂的，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。由于这种新的调节剂如何控制细菌细胞分裂完全未知，我们的目的是a）表征链霉菌和分枝杆菌中调节剂的功能b）确定调节剂如何影响体外FtsZ支架组装的动力学）理解调节剂与FtsZ相互作用的结构基础为了实现这些目的，我们将采用一系列的分子、细胞生物学和生物化学技术，并通过对调节剂本身和与FtsZ复合物的结构解析来补充我们的功能表征研究。

项目成果

Cap-tivating findings provide insight into bacterial cell division: (Trends in Microbiology, 31:3 p:219-221, 2023).

引人入胜的发现提供了对细菌细胞分裂的深入了解：（Trends in Microbiology, 31:3 p:219-221, 2023）。

• DOI: 10.1016/j.tim.2023.02.010
• 发表时间: 2023
• 期刊: Trends in microbiology
• 影响因子: 15.9
• 作者: Sallmen JW

Cap-tivating findings provide insight into bacterial cell division.

引人入胜的发现提供了对细菌细胞分裂的深入了解。

• DOI: 10.1016/j.tim.2023.01.005
• 发表时间: 2023
• 期刊: Trends in microbiology
• 影响因子: 15.9
• 作者: Sallmen JW

Cytoplasmic contractile injection systems mediate cell death in Streptomyces.

• DOI: 10.1038/s41564-023-01341-x
• 发表时间: 2023-04
• 期刊: NATURE MICROBIOLOGY
• 影响因子: 28.3
• 作者: Casu, Bastien;Sallmen, Joseph W.;Schlimpert, Susan;Pilhofer, Martin
• 通讯作者: Pilhofer, Martin