Automated Behavioral Analysis of Large C. elegans Populations Using a Wide Field-of-view Tracking Platform

被引:7
|
作者
Perni, Michele [1 ]
Casford, Sam [1 ]
Aprile, Francesco A. [1 ]
Nollen, Ellen A. [2 ]
Knowles, Tuomas P. J. [1 ]
Vendruscolo, Michele [1 ]
Dobson, Christopher M. [1 ]
机构
[1] Univ Cambridge, Dept Chem, Ctr Misfolding Dis, Cambridge, England
[2] Univ Med Ctr Groningen, European Res Inst Biol Aging, Groningen, Netherlands
来源
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS | 2018年 / 141期
关键词
Immunology and Infection; Issue; 141; Drug discovery; phenotype-based screening; high-throughput screening; C; elegans; amyloid formation; Alzheimer's disease; neurodegeneration; nematode library; large population analysis; BETA-AMYLOID PEPTIDE; PROTEIN HOMEOSTASIS; LIFE-SPAN; AGGREGATION; GENES; IDENTIFICATION; INHIBITION; SCREEN; MODEL;
D O I
10.3791/58643
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Caenorhabditis elegans is a well-established animal model in biomedical research, widely employed in functional genomics and ageing studies. To assess the health and fitness of the animals under study, one typically relies on motility readouts, such as the measurement of the number of body bends or the speed of movement. These measurements usually involve manual counting, making it challenging to obtain good statistical significance, as time and labor constraints often limit the number of animals in each experiment to 25 or less. Since high statistical power is necessary to obtain reproducible results and limit false positive and negative results when weak phenotypic effects are investigated, efforts have recently been made to develop automated protocols focused on increasing the sensitivity of motility detection and multi-parametric behavioral profiling. In order to extend the limit of detection to the level needed to capture the small phenotypic changes that are often crucial in genetic studies and drug discovery, we describe here a technological development that enables the study of up to 5,000 individual animals simultaneously, increasing the statistical power of the measurements by about 1,000-fold compared to manual assays and about 100-fold compared to other available automated methods.
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页数:9
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