Cryo-electron microscopy to study fundamental bacterial processes: bacterial cell division

细菌细胞生物学在过去几年中出现了复兴，部分原因是成像技术的进步。研究人员能够窥视细胞并描述参与基本生物过程的大分子复合物的定位和组织，这推进了我们对细菌细胞如何生长，移动和分裂的理解。荧光显微镜，冷冻电子显微镜（CEM）和冷冻电子断层扫描（CET）的重大进展提供了新的见解，完成这些基本过程的细菌超微结构。现在很明显，与它们的远距离真核生物类似，细菌是高度组织化的细胞，拥有内化的隔间，细胞骨架，有组织的基因组和精心定位的大分子机器。此外，成像技术的进步提供了证据，证明这些细胞系统和组件并不是独立发挥作用，而是通常协同工作，以实现细胞目标。这一点在细菌细胞分裂过程中表现得最为明显，细胞、分子和成像技术的结合开始提供关于这一最基本和最根本的细菌过程的丰富知识。该研究项目旨在使用和开发尖端的冷冻电子显微镜技术，以确定参与细菌细胞分裂的蛋白质复合物的分子结构。我们的长期目标是利用我们对细胞分裂机制的改进知识来确定新的药物靶点，并利用这一基本过程来对抗越来越多的多重耐药菌株。

Bacterial cell biology has seen a renaissance in the past several years that has been spurred in part by advances in imaging techniques. The ability of researchers to peer into cells and describe the localization and organization of macromolecular complexes involved in basic biological processes has advanced our understanding of how bacterial cells grow, move and divide. Major advances in fluorescence microscopy, cryo-electron microscopy (CEM) and cryo-electron tomography (CET) have provided new insight into the bacterial ultrastructures that accomplish these fundamental processes. It is now apparent that not unlike like their distant eukaryotic counterparts, bacteria are highly organized cells that possess internalized compartments, cytoskeletons, organized genomes and carefully positioned macromolecular machines. Furthermore, advances in imaging are providing evidence that these cellular systems and assemblies do not function independently, but generally in concert, to accomplish cellular goals. Nowhere is this more apparent than in the process of bacterial cell division, where the combination of cellular, molecular and imaging techniques are beginning to provided a wealth of knowledge about this most basic and fundamental bacterial process. This research project aims to use and develop cutting-edge cryo-electron microscopy techniques to determine the molecular architecture of protein complexes involved in bacterial cell division. Our long-term goal is to use our improved knowledge of the mechanism of cell division to identify new drug targets and exploit this fundamental process to fight the growing number of multi-drug resistant strains of bacteria.