线虫脂质代谢高通量高内涵RNAi筛选系统的研究

项目名称： 线虫脂质代谢高通量高内涵RNAi筛选系统的研究

项目编号： No.31300701

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 张翔

作者单位： 中国科学院生物物理研究所

项目金额： 22万元

中文摘要： 脂滴是生物体内脂质存储的主要场所，它与对人类代谢疾病的防治和对生物能源的开发直接相关，从原核生物细菌到高等动物人都有脂滴的存在。脂代谢的异常会导致动脉粥样硬化和糖尿病等多种代谢类疾病。基于与高等动物基因的高度同源性以及操作手段的多样性，线虫已成为研究脂代谢的重要模式生物。 利用线虫进行全基因组RNAi筛选，确定调节脂肪代谢的重要基因，对深入理解脂肪调控的分子机制，开发治疗脂类代谢疾病药物具有重要意义。目前常用来做高通量RNAi筛选的设备是Worm Sort，该设备能高通量筛选出荧光强度不同的线虫，但筛选的分辨率较低，不能区分脂滴大小及数量的变化，难以达到脂滴量级的高通量筛选。本项目拟以线虫作为模式动物进行脂质代谢相关研究，并结合显微镜系统、自动控制、模式识别等多种技术研究方法，开发出能够对线虫中脂滴大小及数量变化等进行高通量高内涵RNAi筛选的系统，同时筛选出影响脂质代谢的关键基因。

中文关键词： 高内涵；高通量；RNAi筛选；线虫脂滴；

英文摘要： Lipid droplet is the main place of lipid storage in vivo, and it is directly related to the prevention of the human metabolic diseases and the development of biomass energy. There are lipid droplets from prokaryotic bacteria to higher animals. Abnormal lipid metabolism can cause atherosclerosis, diabetes and other metabolic diseases. C. elegans has become an important model organism for studying lipid metabolism because its diverse means of operation and highly homologous to higher animal genes. The use of C. elegans genome-wide RNAi screening to determine the important genes that regulate fat metabolism, is of greate significance for in-depth understanding of the molecular mechanisms of fat regulation, and development of drug in treatment of lipid metabolism related diseases. Equipment named Worm-Sort is currently used for C. elegans high-throughput RNAi screening, this device is capable of high-throughput screening C. elegans of different fluorescence intensity, but cannot distinguish difference of lipid droplet size and lipid droplet number, Because of poor sensitivity of this device, it is difficult to reach the resolution of lipid droplet level. The project intends to develop a high throughput high content RNAi screening system which can distinguish lipid droplet size and number in C. elegans, to find out t

英文关键词： high-content；high-throughput；RNAi screening；lipid droplet；