Higher-Order RNA Structure and Function in the HIV-1 Genome

HIV-1 基因组中的高阶 RNA 结构和功能

• 批准号: 9064527
• 负责人: Colleen Ann Kellenberger
• 金额: $ 1.82万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-04 至 2016-06-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9064527
• 关键词: AIDS/HIV problem; Antiviral Agents; Binding Sites; Bioinformatics; Classification; Complex; Data; Development; Disease; Drug resistance; Educational process of instructing; Epidemic; Ethics; Evolution; Faculty; Generations; Genetic Code; Genome; Goals; HIV; HIV Infections; HIV-1; Higher Order Chromatin Structure; Indium; Individual; Infection; Intervention; Lead; Leadership; Modeling; Molecular; Nucleotides; Outcome; Pharmaceutical Preparations; Positioning Attribute; Proteins; Public Health; RNA; RNA Folding; RNA Sequences; RNA-Binding Proteins; RNA-Protein Interaction; Reagent; Research; Resolution; Role; Site; Structural Models; Structure; Techniques; Therapeutic; Therapeutic Intervention; Training; Training Programs; Viral; Viral Packaging; Virion; Virus Replication; Work; base; drug resistant virus; experience; gag Gene Products; genetic information; genome-wide; genomic RNA; insight; new therapeutic target; next generation sequencing; novel; novel therapeutic intervention; particle; public health relevance; resistant strain; small molecule therapeutics; therapeutic target; tool; viral RNA; virology

 DESCRIPTION (provided by applicant): The HIV/AIDS epidemic remains a major global public health challenge. Currently 35 million individuals are infected with HIV, and 3 million new infections occur each year. A key challenge in controlling HIV infection is the evolution of drug-resistant strains. New therapeutic strategies are essential to effectively trump viral evolution an eliminate HIV spread. Current retroviral therapies consist of drug cocktails targeting diverse protein-based functions; however, the viral genomic RNA constitutes an unexplored target for viral intervention. Viral replication depends not only on the genetic code contained in the primary sequence, but also on the functional roles of complex high-order RNA structures. If RNA structure is to be an effective therapeutic target, accurate, nucleotide-resolution models of higher-order structures in the RNA genome must be developed. The goal of this proposal is to identify functional motifs in the HIV-1 genomic RNA using cutting-edge computational and experimental approaches. Computational strategies will be developed to identify and characterize RNA-protein interactions essential for viral maturation and to model tertiary structure motifs throughout the entire 9,200 nucleotide HIV-1 genome. Ultimately, this research will lead to novel high-throughput structural modeling strategies for identification of novel therapeutic targets within HIV-1 that can be applied to any disease-related RNA. Through this training program, I will gain expertise in structural analysis techniques, next generation sequencing, bioinformatics, and virology. My long-term goal is to become a leader in RNA-based disease research, and this experience will be critical as I work toward this objective.

 描述（由申请人提供）：艾滋病毒/艾滋病流行病仍然是一个重大的全球公共卫生挑战。目前有3 500万人感染艾滋病毒，每年有300万新感染者。控制艾滋病毒感染的一个关键挑战是耐药性菌株的演变。新的治疗策略对于有效战胜病毒进化和消除艾滋病毒传播至关重要。目前的逆转录病毒疗法由靶向不同蛋白质功能的药物鸡尾酒组成;然而，病毒基因组RNA构成了病毒干预的未开发靶点。病毒的复制不仅依赖于初级细胞中的遗传密码， 序列，但也对复杂的高阶RNA结构的功能作用。如果RNA结构是一个有效的治疗目标，准确的，在RNA基因组中的高阶结构的核苷酸分辨率模型必须开发。该提案的目标是使用尖端的计算和实验方法来识别HIV-1基因组RNA中的功能基序。将开发计算策略来识别和表征病毒成熟所必需的RNA-蛋白质相互作用，并在整个9，200个核苷酸的HIV-1基因组中模拟三级结构基序。最终，这项研究将导致新的高通量结构建模策略，用于识别HIV-1中的新治疗靶点，这些靶点可以应用于任何疾病相关的RNA。通过这个培训项目，我将获得结构分析技术，下一代测序，生物信息学和病毒学方面的专业知识。我的长期目标是成为基于RNA的疾病研究的领导者，这段经历对我实现这一目标至关重要。