Bacterial cell cycle control

细菌细胞周期控制

• 批准号: 7629796
• 负责人: SUSAN THOMAS LOVETT
• 金额: $ 29.22万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7629796
• 关键词: Actins; Address; Affect; Amino Acids; Antibiotic Therapy; Antibiotics; Arts; Bacteria; Binding; Biochemical; Biochemistry; Biogenesis; Biological Assay; Biology; Cell Cycle; Cell Cycle Arrest; Cell Cycle Progression; Cell Cycle Regulation; Cells; Cellular biology; Chromatin; Chromosome Segregation; Chromosome Structures; Chromosomes; Complex; Cytoskeleton; DNA biosynthesis; DNA-Binding Proteins; Data; Escherichia coli; Eukaryotic Cell; Event; Filament; Fluorescence; Fluorescence Microscopy; Genetic; Genetic Screening; Growth; Guanosine Triphosphate Phosphohydrolases; Imagery; Life; Mediating; Microbiology; Microfilaments; Mitochondria; Mutation; Nutrient; Nutritional status; Physiology; Process; Prokaryotic Cells; Property; Proteins; Regulation; Replication Initiation; Ribosomes; Role; SeqA protein; Staging; Starvation; Stress; Structure; Techniques; Testing; Translations; mutant; pathogen; response; segregation; tool

DESCRIPTION (provided by applicant): How cell cycle events are controlled with growth remains an important and perhaps the most important, outstanding question in prokaryotic biology. A group of conserved and essential GTPase proteins, related to Ras, have been implicated in cell cycle control but remain poorly characterized. The study of the Obg GTPase has the potential to elucidate aspects of the mechanism of chromosome segregation in bacteria, which is not, at present, understood. Because Obg is universally conserved and essential, its function has impacts on all bacteria, including bacterial pathogens, and constitutes a potential target for antibiotic therapy. All eukaryotic cells possess Obg, too-its function may be essential for mitochondria-and therefore its role in eukaryotic cell biology will be important to understand and will be facilitated by studies first in prokaryotes. An integrative approach, combining cell visualization, genetics, biochemistry and physiology, provides an opportunity to make headway into understanding these important and complex problems. The connection between translational stress and cell cycle will be investigated. The hypothesis that SeqA binding to the chromosome controls access to replication initiation and chromosome segregation machinery will be tested. Additional factors in the stringent response control of cell cycle will be sought. Using state-of- the-art fluorescence microscopy, the localization of the E. coli Obg protein will be examined, as well as its impact on bacterial cytoskeleton, including the actin-related MreB helical filament, and the organization of the chromosome and replisome. The interaction of the ObgE protein with several proteins, including those controlling replication initiation and chromosome segregation, processes on which Obg may exert control, will be probed. Several genetic screens will explore the role of ObgE and the DNA binding protein, SeqA in the regulation of DNA replication and chromosome segregation. Finally, the association of ObgE with the ribosome will be studied, as well as the impact of the stringent response and ObgE on ribosome function and stability. LAY DESCRIPTION: We will study a protein present in all bacteria that appears to control their growth. This will provide important missing information about how bacteria divide and may provide a target for antibiotics.

描述（由申请人提供）：如何控制细胞周期事件与生长仍然是原核生物学中一个重要的、也许是最重要的、悬而未决的问题。一组与 Ras 相关的保守且必需的 GTP 酶蛋白与细胞周期控制有关，但仍不清楚。对 Obg GTPase 的研究有可能阐明细菌染色体分离机制的各个方面，但目前尚不清楚。由于 Obg 是普遍保守且必需的，因此其功能对所有细菌（包括细菌病原体）都有影响，并构成抗生素治疗的潜在靶点。所有真核细胞也都具有 Obg——它的功能可能对线粒体至关重要——因此理解它在真核细胞生物学中的作用非常重要，并且首先在原核生物中进行研究将有助于理解它。结合细胞可视化、遗传学、生物化学和生理学的综合方法为理解这些重要而复杂的问题提供了一个机会。将研究平移应激和细胞周期之间的联系。 SeqA 与染色体结合控制复制起始和染色体分离机制的假设将得到测试。将寻找细胞周期严格反应控制中的其他因素。使用最先进的荧光显微镜，将检查大肠杆菌 Obg 蛋白的定位，及其对细菌细胞骨架的影响，包括肌动蛋白相关的 MreB 螺旋丝，以及染色体和复制体的组织。 ObgE 蛋白与多种蛋白质的相互作用，包括那些控制复制起始和染色体分离的蛋白质，Obg 可能对这些过程进行控制。一些遗传筛选将探索 ObgE 和 DNA 结合蛋白 SeqA 在 DNA 复制和染色体分离调节中的作用。最后，将研究ObgE与核糖体的关联，以及严格反应和ObgE对核糖体功能和稳定性的影响。简单描述：我们将研究所有细菌中存在的一种蛋白质，该蛋白质似乎可以控制细菌的生长。这将提供有关细菌如何分裂的重要缺失信息，并可能为抗生素提供靶点。