Chromosome Compaction and Cyanobacterial Gene Regulation via a Circadian Clock

本研究的长期目标是更好地了解蓝藻长聚球菌昼夜节律产生和维持的分子机制。这种理解将包括生物钟用作时间标记的代谢信号，体内生物钟机制本身以及生物钟控制的基因表达和代谢的节律模式。最近，生物钟调节的染色体压实被确定为生物钟产生的基因表达节律的一个组成部分。生物钟似乎利用这种压缩节奏来建立生物钟调节的基因表达模式之间的节奏模式和相位关系。然而，这一假设需要更严格的实验测试来证实。此外，先前发现，缺乏关键蛋白功能的菌株，SasA蛋白，尽管继续具有生物钟功能，但仍会失去正常的基因表达模式。最近的证据表明，染色体压实节律和SasA蛋白功能都是必要的，但对于基因表达昼夜节律的产生和维持都不是充分的。研究的目的是解决染色体压实节律的本质，昼夜节律振荡器组成部分的特定变化如何影响其与SasA蛋白的相互作用，以及这两个生物钟控制过程，染色体压实和SasA功能，如何共同产生和维持整个长叶螺染色体的基因表达节律模式。更广泛的影响本科生、研究生和研究生将参与研究的各个方面。一个典型的学生项目包括基因克隆，蓝藻菌株构建，蛋白质纯化和测定，活细胞的反褶积荧光显微镜。作为培训的一部分，学生还将向广大受众交流和传播他们的研究成果。他们将在每周的实验室会议上与其他专业科学家会面，讨论他们研究进展的细节。他们还将在犹他大学生物系和医学院的微生物学家参加的每周科学期刊俱乐部上讨论他们的研究成果。研究生和研究生将在生物节律研究学会和细菌运动和信号转导小组的会议上展示他们的工作。这些是非常不同类型的科学会议。前者由医学临床医生参加，并使学生接触到他们在昼夜节律生物学方面的研究成果对人类的影响。后者由领先的信号转导小组参加，并使学生接触到最好的科学研究。犹他州的生物系继续招收当地的高中生进入研究实验室，国家科学基金会的资金将支持将他们的老师带入研究实验室环境的努力。

Intellectual MeritThe long-term objective of this research is to better understand the molecular mechanisms underlying circadian rhythm generation and maintenance in the cyanobacterium Synechococcus elongatus. This understanding will include the metabolic signals used as time markers by the circadian clock, the in vivo clock mechanism itself and the rhythmic patterns of gene expression and metabolism controlled by the circadian clock. Recently, clock-regulated chromosome compaction was identified as a component of clock-generated gene expression rhythms. The circadian clock appears to use this compaction rhythm to establish the rhythmic patterns and phase relationships among clock regulated gene expression patterns. However, this supposition requires more rigorous experimental testing for confirmation. In addition, it was previously found that strains devoid of a critical protein function, SasA protein, lose normal patterns of gene expression despite continued circadian clock function. Recent evidence demonstrates that chromosome compaction rhythms and SasA protein function are each necessary but neither one is sufficient for the generation and maintenance of circadian rhythms in gene expression. The research objectives address the nature of the chromosome compaction rhythm, how specific changes that occur in components of the circadian oscillator affect its interactions with the SasA protein, and how these two circadian clock controlled processes, chromosome compaction and SasA function, work together to generate and maintain rhythmic patterns of gene expression throughout the entire S. elongatus chromosome.Broader ImpactUndergraduate, graduate, and post graduate students will participate in all aspects of the research. A typical student project includes gene cloning, cyanobacterial strain construction, protein purification and assay, and deconvolution fluorescence microscopy of live cells. As part of their training students will also communicate and disseminate their research results to broad audiences. They will meet with other professional scientists during weekly lab meetings to discuss the details of their research progress. They will also discuss their research results during a weekly scientific journal club attended by microbiologists from the University of Utah's Biology Department and School of Medicine. Graduate and post-graduate students will present their work at meetings of the Society for Research on Biological Rhythms and of the Bacterial Locomotion and Signal Transduction group. These are very different types of scientific meetings. The former is attended by medical clinicians and exposes the students to the human impact of their research efforts in circadian biology. The latter is attended by leading signal transduction groups and exposes students to the best of scientific research. The Biology Department at Utah continues to recruit local high school students into research laboratories and funding from the NSF will support efforts to also bring their teachers into the research laboratory environment.