Targeting Protein Function in Vivo using Small Interfering Proteins (SIPs)

使用小干扰蛋白 (SIP) 靶向体内蛋白质功能

• 批准号: 1046863
• 负责人: James Mahaffey
• 金额: $ 29.81万
• 依托单位: North Carolina State University
• 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: 2010-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1046863&HistoricalAwards=false
• 关键词: Targeting; Protein; Function; Vivo; using

The ability to interfere with gene function is a common technique used to infer the role of genes in animals and plants. However, current technologies for disrupting gene function suffer from several limitations. For example, gene knockouts completely eliminate production of the protein coded by the gene. Consequently, it is difficult to eliminate a single function of multi subunit, multifunctional proteins or to target modified forms of a protein. Cellular processes are often mediated by chemical modifications to proteins, such as addition of a phosphate moiety. In this project, the investigators will evaluate the use of Small Interfering Proteins (SIPs) to specifically interfere with protein function, or parts thereof, in the fruit fly Drosophila melanogaster. SIPs are small proteins that have been engineered to bind to specific domains of the targeted protein with high specificity and affinity. When SIPs bind to specific regions of target proteins, they should disrupt protein function. The investigators will express synthetic genes encoding SIPs targeting test proteins to evaluate the ability and use of SIPs to selectively target protein function in whole organism. If successful, SIPs will provide a valuable set of tools to study the molecular mechanisms underlying cellular function. These tools are expected to greatly improve our understanding of the biology of development.

干扰基因功能的能力是一种常用的技术，用于推断动物和植物基因的作用。然而，目前破坏基因功能的技术存在一些局限性。例如，基因敲除完全消除了由基因编码的蛋白质的产生。因此，很难消除多亚基、多功能蛋白质的单一功能或靶向蛋白质的修饰形式。细胞过程通常是通过对蛋白质的化学修饰来介导的，比如添加一个磷酸基团。在这个项目中，研究人员将评估小干扰蛋白（SIPs）在果蝇中特异性干扰蛋白质功能或其部分功能的使用。SIPs是一种小蛋白，它被设计成以高特异性和亲和力结合到目标蛋白的特定区域。当SIPs结合到靶蛋白的特定区域时，它们会破坏蛋白质的功能。研究人员将表达编码SIPs靶向测试蛋白的合成基因，以评估SIPs在整个生物体中选择性靶向蛋白质功能的能力和使用。如果成功，SIPs将为研究细胞功能的分子机制提供一套有价值的工具。这些工具有望大大提高我们对发育生物学的理解。