Biomolecular Condensates as Organizers of Bacterial RNA Biology

项目摘要 细菌细胞的基本观点是，它们没有组织，因为它们通常 缺乏膜结合的细胞器。尽管教科书上认为细菌是 无组织的，一个不断增长的非膜结合的细胞器阵列，称为“生物分子” 已识别出“冷凝物”。这些冷凝物是通过物理 具有选择性组织酶的能力 和底物进入不同的亚细胞位置，这表明细菌细胞可能是高度 有组织的。Schrader实验室在细菌C中鉴定出了第一个细菌冷凝物。 新月体，被称为BR体，它被发现组织细菌RNA衰变 机械，促进其复杂的多步生化途径。生物信息学签名 BR体已经在包括许多病原体在内的细菌中被鉴定出来，这表明它们是 广泛保存。此外，几种细菌生物分子凝聚物随后 已被确定参与不同的生化途径，这表明细菌细胞 通常由非膜结合的细胞器组织，但细胞器的数量和多样性 这种结构的特征仍然很差。通过结合体内成像实验和 在体外生物化学中，我们试图定义生物分子凝聚体功能的重要方面 和细菌的多样性。我们认为C.新月形BR- 将在病原体中共享，可能导致识别新的 抗生素靶点

PROJECT SUMMARY The fundamental view of bacterial cells is that they are not organized because they generally lack membrane-bound organelles. Despite the textbook perception that bacteria are disorganized, a growing array of non-membrane-bound organelles called “biomolecular condensates” have been identified. These condensates are formed through the physical process of liquid-liquid phase separation and have the capacity to selectively organize enzymes and substrates into distinct subcellular locations, suggesting bacterial cells may be highly organized. The Schrader lab identified the first bacterial condensate in the bacterium C. crescentus, termed the BR-body, which was found to organize the bacterial RNA decay machinery, facilitating its complex multi-step biochemical pathway. Bioinformatic signatures of BR-bodies have been identified across bacteria including many pathogens, suggesting they are broadly conserved. In addition, several bacterial biomolecular condensates have subsequently been identified that are involved in diverse biochemical pathways, suggesting that bacterial cells are generally organized by non-membrane-bound organelles, yet the number and diversity of such structures remains poorly characterized. By combining in vivo imaging experiments and in vitro biochemistry we seek to define the important aspects of biomolecular condensate function and diversity in bacteria. We believe that many of the characteristics of C. crescentus BR- bodies will be shared in pathogenic organisms, potentially leading to the identification of new antibiotic targets.