Collaborative Research: CDI-Type II: Probing Complex Dynamics of Small Interfering RNA (siRNA) Transfection by Petascale Simulations and Network Analysis

合作研究：CDI-Type II：通过 Petascale 模拟和网络分析探索小干扰 RNA (siRNA) 转染的复杂动力学

• 批准号: 1124962
• 负责人: Ananth Grama
• 金额: $ 36万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1124962&HistoricalAwards=false
• 关键词: Collaborative; Research; CDI; Type; II

The discovery of RNA interference mediated gene silencing by double-stranded RNA is one of the most exciting recent developments in the biological and biomedical sciences. RNAi utilizes a pathway whereby a double-stranded small interfering RNA (siRNA) targets and destroys complementary mRNA in eukaryotic cells to regulate gene expression. Since its discovery just over a decade ago scientists have investigated the potential use of siRNA-based treatment of many diseases such as cancer, liver cirrhosis, hepatitis B, human papillomavirus, and hypercholesterolemia. In principle, siRNA has much broader therapeutic applications than other types of drugs because siRNA can be synthetically designed to silence any gene via the RNAi machinery. Therefore, the primary challenge for therapeutic applications is efficient and non-toxic delivery of siRNA to cells within tissues of interest. The research goal of this CDI project is to design efficient delivery systems for siRNA via supercomputer simulations. Multimillion-atom simulations are performed to study: (1) the effect of siRNAs on the molecular structure of lipid membranes and how structural changes affect the membrane permeability; (2) molecular mechanisms by which siRNA molecules attached to gold nanoparticles cross the membrane and go into a cell; and (3) delivery of siRNAs encapsulated in liposomes by ultrasound. Computational technologies will be used to enable automated design of efficient siRNA delivery systems. This project is promoting scholastic and professional excellence among students. A dual-degree program has been established which gives students the opportunity to obtain a Ph.D. in the physical sciences or an engineering discipline and an M.S. in computer science with specialization in high performance computing and simulations. This research team will also organize computational science workshops for undergraduate students and faculty mentors from Historically Black Colleges and Universities and Minority Serving Institutions.

双链RNA介导的RNA干扰基因沉默的发现是生物学和生物医学科学中最令人兴奋的最新进展之一。RNAi利用双链小干扰RNA（siRNA）靶向并破坏真核细胞中的互补mRNA以调节基因表达的途径。自从十多年前发现siRNA以来，科学家们已经研究了基于siRNA的治疗许多疾病的潜在用途，例如癌症、肝硬化、乙型肝炎B、人乳头瘤病毒和高胆固醇血症。原则上，siRNA比其他类型的药物具有更广泛的治疗应用，因为siRNA可以通过RNAi机制合成设计以沉默任何基因。因此，治疗应用的主要挑战是将siRNA有效且无毒地递送至感兴趣的组织内的细胞。该CDI项目的研究目标是通过超级计算机模拟设计有效的siRNA递送系统。进行了数百万个原子的模拟，以研究：（1）siRNA对脂质膜的分子结构的影响以及结构变化如何影响膜渗透性;（2）附着在金纳米颗粒上的siRNA分子穿过膜并进入细胞的分子机制;以及（3）通过超声递送封装在脂质体中的siRNA。计算技术将用于实现高效siRNA递送系统的自动化设计。该项目正在促进学生的学业和专业卓越。建立了双学位课程，使学生有机会获得博士学位。在物理科学或工程学科和硕士学位。计算机科学专业，擅长高性能计算和模拟。该研究小组还将为来自历史上黑人学院和大学以及少数民族服务机构的本科生和教师导师组织计算科学研讨会。