Small proteins in sugar metabolism

描述(申请人提供)：新陈代谢控制是每个有机体生存的关键。尽管进行了多年的研究，但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巨大作用。此外，新的数据表明，即使是对大肠杆菌来说，它们首选的营养来源也存在菌株之间的差异。大部分 这种变异似乎与菌株所栖息的生态位有关，无论是肠道、尿路还是实验室。那么，这些菌株如何控制自己的新陈代谢，从而有效地利用营养呢？我们已经在病原菌O157：H7 EDL933中确定了一个遗传基因座，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，前者编码高度疏水的29个氨基酸蛋白质，后者编码反义小RNA，抑制ZOR基因的表达。EDL933中全部四个基因位点的缺失会导致许多代谢物水平的改变和基因表达的全球变化。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，我们假设Zor-orz基因参与了细胞新陈代谢的控制。在这个建议中，我们将通过研究ZOR基因的表达如何受到细胞和其他元素的营养状态的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识别与ZOR相互作用的蛋白质来探索该基因座的功能(目标2)。这些方法结合在一起，将有助于解开Zor-orz基因座的生物学作用，并有助于理解生物如何控制新陈代谢过程。更广泛地说，这些实验将提供关于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的见解。

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.