Excellence in Research: MicroRNA Detection Strategies via Exploration of Flavin Binding Allosteric Switches

卓越研究：通过探索黄素结合变构开关的 MicroRNA 检测策略

• 批准号: 2100898
• 负责人: Mehnaaz Ali
• 金额: $ 35.4万
• 依托单位: Xavier University of Louisiana
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2100898&HistoricalAwards=false
• 关键词: Excellence; Research; MicroRNA; Detection; Strategies

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Mehnaaz F. Ali of Xavier University of Louisiana is studying the design and exploration of flavin induced allosteric aptamers with microRNA specific functional domains. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are biologically active forms of riboflavin. These molecules play diverse and wide-ranging roles in a multitude of biological processes due to their structure and chemical versatility. The exploration of FAD and their interactions as ligands within allosteric nucleic acid probes will offer fundamental insight into their potential role as molecular switches, chemo-responsive sensors or genetic control elements. In addition to promoting discovery in nucleic acid chemistry and sensing fields, this project (both directly and indirectly-via Dr. Ali’s teaching responsibilities and outreach program) will also promote teaching, and learning of chemistry at the middle school through undergraduate level. RNA polymers are well known for their ability to present a range of distinct structural conformations. These molecules lend themselves to the formation of allosteric nucleic acid scaffolds with multiple binding domains. Although ubiquitous in nature, the isolation of molecules with dual-domain functionality from a random sequence population is not facile. An approach to generating allosteric ribozymes is to utilize a mixture of modular rational design in combination with in-vitro selection strategies. To explore the utility of flavins as ligands, Dr. Ali is interested in using a combination of these existing efforts to design allosteric systems by using rational design to construct flavin dependent conformational switches, where flavin binding will lead to the formation of binding pockets using an aptamer scaffold with tailored miR binding regions. Such forms of ‘adaptive-binding’ have traditionally been used with RNA motifs to allosterically regulate the activity of naturally occurring catalytic RNA. Together, these systems provide novel approaches to chemo-responsive sensing, particularly novel methods of allosteric aptamer development. Specifically, these studies are expected to contribute to the design of new flavin binding scaffolds for sensing microRNA.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学过程中的化学过程（CLP）方案的支持下，路易斯安那州Xavier大学的Mehnaaz F. Ali正在研究Flavin诱导的具有MicroRNA特定功能领域的变构适体的设计和探索。黄素单核苷酸（FMN）和黄素腺嘌呤二核苷酸（FAD）是核黄素的生物活性形式。这些分子由于其结构和化学多功能性，在多种生物过程中扮演潜水员和广泛的角色。对变构核酸问题中的配体的FAD及其相互作用的探索将为它们作为分子开关，化学反应性传感器或遗传控制元件的潜在作用提供基本洞察力。除了促进核酸化学和感官领域的发现外，该项目（直接和间接宣传阿里博士的教学责任和外展计划）还将通过本科层面促进中学的教学和学习化学。 RNA聚合物以其提供一系列不同结构考虑的能力而闻名。这些分子将自己的变构核酸支架形成具有多个结合结构域。尽管本质上无处不在，但从随机序列种群中分离具有双域功能的分子并不容易。产生变构核酶的一种方法是将模块化理性设计的混合物与体外选择策略结合使用。为了探索黄素作为配体的实用性，Ali博士有兴趣通过使用理性设计来结合这些现有努力来设计变构系统，以构建依赖黄素的会议开关，其中黄素结合将导致使用量身定制的MIR结合区域使用APATER APATER -APATER的结合口袋形成。传统上，这种形式的“适应性结合”已与RNA基序一起使用，以变构调节天然发生的催化RNA的活性。这些系统共同提供了用于化学响应灵敏度的新方法，尤其是变构酸反应发展的新方法。具体而言，这些研究有望有助于新的黄素结合支架的设计用于传感microRNA。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响评估标准来评估值得支持。