A Device for Automated Large-Scale Morphological and Behavioral Screening

该奖项支持开发一种计算机驱动的自动化设备，用于筛选涡虫小分子文库。原理验证装置将由大约100个细胞组成，每个细胞包含一个单一的涡虫和一个待筛选的库元素。每个细胞将通过数码相机观察和分析蠕虫的行为和形态，并通过改变光照水平和轻微电击对某些行为进行奖励/惩罚。这些细胞将由计算机连续分析和控制，计算机将筛选特定的结果（例如，筛选库中的试剂，以增加蠕虫的运动能力，改变头部发育，抵消毒素的影响，或加快操作性条件反射的学习速度）。计算机将检测形态、行为和其他参数的变化。该设备的最初开发将集中在涡虫上，但最终版本将对许多生物有用（包括携带荧光报告基因的转基因生物，用于分析特定性状）。它将能够筛选小分子、RNAi、蛋白质、抗体等文库。要寻找的潜在目标包括：改善记忆，增加或减少运动活动，改变神经元生长，抵消已知药物的作用，增强或抑制感觉模式，改变再生过程中的形态，延缓衰老，加速或减速新陈代谢，或作为已知有毒化合物的抗毒素的试剂。

This award supports the development of a computer-driven, automated device for screening libraries of small molecules on planaria. The proof-of-principle device will consist of about 100 cells, each containing a single planarian and one element of the library to be screened. Each cell will provide for observation and analysis of worm behavior and morphology via a digital camera and for the reward/punishment of certain behaviors by modification of light levels and mild electric shock. The cells will be continuously analyzed and controlled by a computer which will screen for specified results (for example, screening the library for a reagent which increases worm motility, alters head development, counteracts the effects of toxins, or accelerates the rate of learning in operant conditioning). The computer will detect changes in morphology, behavior, and other parameters. Initial development of the device will be focused on planaria, but the final version will be useful for many organisms (including transgenics carrying fluorescent reporters for analysis of specific traits). It will enable screening of libraries of small molecules, RNAi, proteins, antibodies, and others. Potential targets to be searched for include reagents which: improve memory, increase or decrease motor activity, modify neuronal growth, counteract effects of known drugs, enhance or dampen sensory modalities, alter morphology during regeneration, slow aging, accelerate or decelerate metabolism, or act as an anti-toxin to known poisonous compounds.