EAGER: Rapid Enrichment, Sequencing, and Assembly of Targeted Genomic DNA

EAGER：目标基因组 DNA 的快速富集、测序和组装

• 批准号: 0964859
• 负责人: Michael Axtell
• 金额: $ 10.29万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2012-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0964859&HistoricalAwards=false
• 关键词: EAGER; Rapid; Enrichment; Sequencing; Assembly

Intellectual Merit: Genes are the fundamental unit of biological information. Most genes are discrete segments of DNA which are "expressed" by being used as the templates for RNA production (a process known as transcription); subsequent decoding of the RNA (a process known as translation) results in the production of a protein with a defined function in the cell. Control of gene expression is critical for all organisms; regulation of the initiation of transcription is a critical step at which gene expression is controlled. Regions of DNA flanking transcribed genes often contain short sequences termed cis-regulatory elements (CREs). CREs are bound by proteins which in turn control initiation of transcription from the neighboring gene; this binding typically requires defined DNA sequences within the CREs. CREs which are important maintain a constant sequence over evolutionary time, while the other DNA surrounding them is unconstrained and drifts in sequence. Thus, a powerful method to identify important CREs is to align DNA sequences flanking transcribed genes from multiple, related species. A major technical bottleneck of this approach is determining the flanking DNA sequences themselves. This project seeks to develop a rapid and flexible method to quickly determine the DNA sequence surrounding a gene of interest in multiple species.Broader Impacts: This project involves the training of a female Ph.D. student, and as such, addresses the need to broaden inclusion of women in the Science, Technology, Engineering, and Mathematics (STEM) fields. The methodology itself has the potential to catalyze the discovery of multiple CREs for critical genes. The resulting understanding of gene regulation may in turn have positive impacts in many areas of the biological sciences, as well as potential practical applications in biotechnology.

智力价值：基因是生物信息的基本单位。大多数基因都是离散的DNA片段，通过用作RNA生产的模板(称为转录过程)来“表达”；随后对RNA进行解码(称为翻译过程)，导致在细胞中产生具有特定功能的蛋白质。基因表达的控制对所有生物体来说都是至关重要的；转录启动的调控是基因表达控制的关键步骤。转录基因两侧的DNA区域通常含有被称为顺式调节元件(Cres)的短序列。Cres与蛋白质结合，进而控制邻近基因转录的启动；这种结合通常需要在Cres中定义DNA序列。重要的CRE在进化过程中保持一个恒定的序列，而它们周围的其他DNA是不受限制的，在序列中漂移。因此，识别重要的Cres的一个有效方法是将来自多个相关物种的转录基因两侧的DNA序列进行比对。这种方法的一个主要技术瓶颈是确定侧翼DNA序列本身。该项目旨在开发一种快速、灵活的方法来快速确定多个物种中感兴趣的基因周围的DNA序列。广泛影响：该项目涉及对一名女性博士生的培训，并因此满足了在科学、技术、工程和数学(STEM)领域扩大女性包容性的需要。该方法本身具有催化发现关键基因的多个CRE的潜力。由此产生的对基因调控的理解可能反过来对生物科学的许多领域产生积极影响，以及在生物技术中的潜在实际应用。