Small proteins in sugar metabolism

描述（由申请人提供）：代谢控制是每种生物生存的关键。尽管经过多年的研究，新发现的基因在细菌中在控制新陈代谢方面发挥着重要作用。此外，新的数据表明，即使是大肠杆菌，在其首选的营养来源中也存在菌株间的差异。大部分 这种变异似乎与菌株所处的生态位有关，无论是在肠道、泌尿道还是在实验室中。那么，这些菌株是如何控制它们的新陈代谢，从而有效地利用营养物质的呢？我们已经确定了病原体E中的一个遗传位点，zor-orz位点。coliO 157：H7EDL 933。zor-orz基因座由两个zor基因和两个orz基因组成，所述两个zor基因编码高度疏水的29个氨基酸的蛋白质，所述两个orz基因编码抑制zor基因表达的反义小RNA。在EDL 933中缺失整个四基因位点导致许多代谢物水平的改变和基因表达的整体变化。我们的数据还表明zor基因的表达受细胞的营养状态的调节。结合这些观察结果，我们假设zor-orz基因座参与细胞代谢的控制。在这个提议中，我们将通过研究zor基因的表达如何受细胞和其他元素的营养状态的调节来探索这一假设（目的1）。我们还将通过确定其对基因表达的影响，研究这些菌株的代谢差异，这些缺失对大分子合成的影响以及识别与Zors相互作用的蛋白质来探索该位点的功能（目的2）。结合起来，这些方法将有助于解开zor-orz基因座的生物学作用，并有助于理解生物体如何控制代谢过程。更广泛地说，这些实验将深入了解细菌如何适应新的生态位，以及如何在自己的环境中保持立足点。

DESCRIPTION (provided by applicant): Metabolic control is key for the survival of every organism. Despite years of studies, newly identified genes have been discovered in bacteria that play a great role in controlling metabolism. Additionally, new data suggests that even for Escherichia coli, there is strain-to- strain variation in their preferred nutrient sources. Much of this variation appears linked to the niche the strain inhabits, whether it is the intestine, urinar tract, or in the laboratory. How then do these strains control their metabolism so that they use nutrients efficiently? We have identified a genetic locus, the zor-orz locus, within the pathogen E. coli O157:H7 EDL933. The zor-orz locus is comprised of two zor genes, which encode highly hydrophobic, 29 amino acid proteins, and two orz genes, which encode antisense, small RNAs that repress zor gene expression. Deletion of the entire four-gene locus in EDL933 leads to altered levels of many metabolites and global changes in gene expression. Our data also suggests that zor gene expression is regulated by the nutritional status of cell. Combining these observations, we hypothesize that the zor-orz locus is involved in the control of cellular metabolism. Within this proposal, we will explore this hypothesis by examining how zor gene expression is regulated by the nutrient status of the cell and other elements (Aim 1). We will also explore the function of this locus by determining its effect on gene expression, examining the metabolic differences of these strains, the effects of these deletions on macromolecular synthesis and identifying proteins that interact with the Zors (Aim 2). Combined, these approaches will help unravel the biological role of the zor-orz locus and aid in understanding how organisms control metabolic processes. More broadly, these experiments will provide insights into how bacteria adapt to new niches as well as maintain their foothold on their own environment.