Small proteins in sugar metabolism

描述（由申请人提供）：代谢控制是每个生物体生存的关键。经过多年的研究，人们在细菌中发现了新发现的基因，这些基因在控制新陈代谢方面发挥着重要作用。此外，新数据表明，即使对于大肠杆菌，其偏好的营养源也存在菌株间差异。很多 这种变异似乎与菌株所处的生态位有关，无论是肠道、尿道还是实验室。那么这些菌株如何控制它们的新陈代谢，以便它们有效地利用营养物质呢？我们在病原体大肠杆菌 O157:H7 EDL933 中鉴定出了一个基因位点，即 zor-orz 基因座。 zor-orz 基因座由两个 zor 基因和两个 orz 基因组成，其中两个 zor 基因编码高度疏水性的 29 个氨基酸蛋白质，而两个 orz 基因编码抑制 zor 基因表达的反义小 RNA。 EDL933 中整个四基因位点的删除会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 基因表达受到细胞营养状况的调节。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。在本提案中，我们将通过检查 zor 基因表达如何受细胞和其他元素的营养状态调节来探索这一假设（目标 1）。我们还将通过确定该基因座对基因表达的影响、检查这些菌株的代谢差异、这些缺失对大分子合成的影响以及鉴定与 Zors 相互作用的蛋白质来探索该基因座的功能（目标 2）。结合起来，这些方法将有助于揭示 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.