Functional Genomics of the Biotin Metabolic Network of Arabidopsis

智力优势：生物素是一种基本分子，其主要功能被认为是参与各种新陈代谢过程的酶所需的催化辅因子。最近的研究表明，生物素也是一种调节分子，似乎在控制基因表达的转录和转录后机制中发挥着关键作用。本研究将以拟南芥为模型，鉴定和表征与真核生物的生物素代谢网络相关的基因的生化和生理功能。植物非常适合于这些研究，因为它们和一些微生物是能够从头合成这种分子的主要生物；所有其他生物都必须从它们的食物或环境中获得这种分子。这个项目将描述生物素代谢网络的一些方面，这些方面是被研究的生物体所特有的，也就是拟南芥，作为模式植物。具体地说：1)发育和环境线索如何调节生物素的生物合成；这些研究将利用研究人员最近发现的两个生物素生物合成基因：BIO1和BIO2；以及2)植物特有的含有生物素的蛋白质的生化和生理功能是什么。这些是甲基巴豆酰-辅酶A羧基酶(由基因at1g03090和at4g34030编码)，种子特有的生物素蛋白(由基因at2g42560编码)，以及三个类似生物素载体的蛋白质(由基因at1g52670，at3g15690，at3g56130编码)；以及3)生物素在转录和转录后水平调节基因表达的机制是什么。将提供实验室内的研究经验，让年轻科学家接触到功能基因组学和生物技术方面的多学科基础研究。这项研究将定义围绕生物素的催化和调节功能构建的复杂代谢网络的组织。这一成果将为如何监管这种复杂的网络提供新的见解。我们的目标是开发一个例子，说明如何将新陈代谢视为一个复杂的综合网络，而不是经典的教科书模型，即一系列线性途径。这种新陈代谢观点的发展只有在其基因组完全测序的有机体的背景下才是可能的。为了全面了解代谢过程如何受到发育和环境因素的交互调节，需要对新陈代谢有这样的了解。

Intellectual merit: Biotin is an essential molecule, whose primary function has been ascribed as a catalytic cofactor required by enzymes involved in diverse metabolic processes. Recent studies indicate that biotin is also a regulatory molecule that appears to play critical roles in controlling transcriptional and post-transcriptional mechanisms in gene expression. This research will identify and characterize the biochemical and physiological functions of genes associated with the biotin metabolic network of eukaryotic organisms, using Arabidopsis as a model. Plants are ideally suited for these studies as they, along with some microbes, are the primary organisms that can synthesize this molecule de novo; all other organisms must acquire this molecule from their diets or from the environment. This project will characterize aspects of the biotin metabolic network that are unique to the organism under study, namely Arabidopsis, as a model plant. Specifically: 1) how do developmental and environmental cues regulate biotin biosynthesis; these studies will take advantage of the two biotin biosynthetic genes that have recently been identified by the investigators, BIO1 and BIO2; and 2) what is the biochemical and physiological function of plant-specific biotin-containing proteins. These are methylcrotonyl-CoA carboxylase (encoded by genes At1g03090 and At4g34030), the seed-specific biotin protein (encoded by gene At2g42560), and three biotin carrier-like proteins (encoded by genes At1g52670, At3g15690, At3g56130); and 3) what are the mechanisms by which biotin regulates gene expression at both the transcriptional and post-transcriptional level.Broader impact: The project will be a vehicle for the education and training of a new cadre of scientists at the undergraduate, graduate and post-graduate levels. In-lab research experiences will be provided for exposing young scientists to multidisciplinary basic research in functional genomics and biotechnology. The research will define the organization of a complex metabolic network that is structured around the catalytic and regulatory functions of biotin. This achievement will provide novel insights into how such complex networks are regulated. The goal is to develop an example of how to view metabolism as a complex integrated network rather than the classical textbook model of a set of linear pathways. The development of this view of metabolism is possible only in the context of an organism whose genome is completely sequenced. Such an understanding of metabolism is required in order to comprehensively understand how metabolic processes are interactively regulated by developmental and environmental cues.