Deciphering the molecular circuitry that controls cell cycle progression in bacteria

破译控制细菌细胞周期进程的分子电路

• 批准号: 10227369
• 负责人: Paola E Mera
• 金额: $ 29.3万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-05 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227369
• 关键词: Address; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Model; Binding; Biological Models; Carbon; Caulobacter crescentus; Cell Cycle; Cell Cycle Progression; Cell Cycle Regulation; Cell Size; Cell Survival; Cell division; Cell physiology; Cells; Centromere; Chromosome Segregation; Chromosomes; Complex; Cytokinesis; DNA biosynthesis; Data; Defect; Dependence; Development; Drug Targeting; Event; Genetic; Genetic Transcription; Goals; Health; Link; Maintenance; Metabolic; Metabolism; Modeling; Molecular; Molecular Target; Nutrient; Outcome; Process; Protein Dynamics; Proteins; Proteomics; Publishing; Regulation; Regulation of Cell Size; Replication Initiation; Resistance; Role; Testing; Variant; base; cell type; chromosome replication; design; event cycle; genome integrity; insight; novel; prevent; segregation; temporal measurement; transcriptomics; z-ring

Maintaining the integrity of the genome is essential to cell survival. To accomplish this vital task, major cell cycle events including chromosome replication, segregation, and proper timing of cytokinesis are exquisitely coordinated, temporally and spatially. Any defect that disturbs this coordination can be lethal. Although replication, segregation, and cell division have been extensively studied in bacteria, our understanding of how these processes are coordinated remains limited. Bacteria’s survival also depends on their ability to coordinate cell cycle progression with environmental fluctuations. In this project, we focus on the conserved chromosome replication initiator protein DnaA and its non-replicative functions. The long-term goal is to characterize the molecular functions of regulators that coordinate the progression of the cell cycle and thus represent potential drug targets. The overall objective of this project is to define the mechanisms used to temporally coordinate the onset of chromosome replication with the progression of the cell cycle using the bacterial model system Caulobacter crescentus. The central hypothesis is that DnaA controls the activity of key regulators involved in chromosome segregation and cell size determination. The focus of Aim 1 is to define how DnaA coordinates chromosome replication with the onset of segregation by characterizing the physical association of DnaA with the chromosomal locus the centromere over the cell cycle. The focus of Aim 2 is to define the molecular network that links DnaA’s activity to cell size regulation and its dependency on nutrient availability. Information garnered from this project will provide valuable insights into strategies used by bacteria to temporally and spatially coordinate the multiple mechanisms that are fundamental for the cell survival.

维持基因组的完整性对细胞存活至关重要。为了完成这个重要的任务，主要的细胞