EAGER: Toward a tractable genetic model of DNA virus - Drosophila interaction

EAGER：建立 DNA 病毒与果蝇相互作用的易处理遗传模型

• 批准号: 2135167
• 负责人: Robert Unckless
• 金额: $ 25.36万
• 依托单位: University of Kansas Center for Research Inc
• 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: 2021-08-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2135167&HistoricalAwards=false
• 关键词: EAGER; Toward; tractable; genetic; model

DNA viruses are a difficult problem in health care and a widely-used tool for managing pest populations, particularly in agriculture. However, researchers lack good models to study the interactions between DNA viruses and their hosts. This project aims to create a tractable genetic model for studying host/DNA virus interaction using fruit flies (Drosophila), one of the most widely used model organisms. This advance would allow for genetic manipulation of the virus through standard laboratory techniques to better understand the molecular genetic basis of virulence, host manipulation, and the emergence and evolution of infectious disease. Researchers will also optimize the growth of the nudivirus in cell lines, making possible a drove of experiments in the future. In addition, the project would train undergraduate researchers from a transfer student program to provide them with hands-on scientific training and contribute to broadening participation in science. The first objective is to create new cell lines and optimize conditions for viral replication. To date available cell lines have been used to grow the virus with limited success. Utilizing new cell lines based on natural host tissues and optimized conditions promises to improve viral replication in cell lines. The second objective is to clone the large, double stranded DNA genome into a bacterial artificial chromosome for ease of production, then show that genetic manipulation of the virus is straightforward using standard site-directed mutagenesis and PCR-based recombinant techniques. Upon project completion, researchers will have developed a versatile, tractable system for studying host/DNA virus coevolution that can be used to inform treatment of DNA virus diseases and biocontrol strategies.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.

DNA病毒是卫生保健中的一个难题，也是管理害虫种群的一种广泛使用的工具，特别是在农业中。然而，研究人员缺乏良好的模型来研究DNA病毒与宿主之间的相互作用。该项目旨在利用果蝇(果蝇)创建一个易于处理的遗传模型，用于研究宿主/DNA病毒的相互作用。果蝇是应用最广泛的模式生物之一。这一进展将允许通过标准的实验室技术对病毒进行基因操作，以更好地了解毒力、宿主操作以及传染病的出现和进化的分子遗传学基础。研究人员还将优化纽瓦拉在细胞系中的生长，使未来的实验成为可能。此外，该项目将从转学计划中培训本科生研究人员，为他们提供实践科学培训，并为扩大对科学的参与做出贡献。第一个目标是创造新的细胞系并优化病毒复制的条件。到目前为止，已有的细胞系被用于培养这种病毒，但成效有限。利用基于自然宿主组织和优化条件的新细胞系有望改善细胞系中的病毒复制。第二个目标是将大的双链DNA基因组克隆到细菌人工染色体中，以便于生产，然后使用标准的定点突变和基于PCR的重组技术证明对病毒的遗传操作是直接的。项目完成后，研究人员将开发出一种通用、易处理的系统，用于研究宿主/DNA病毒的共同进化，可用于为DNA病毒疾病的治疗和生物防治策略提供信息。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。