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，用于筛选舟形藻上的小分子文库。原理证明装置将由大约100个细胞组成，每个细胞包含一个单独的脊椎动物和一个待筛选的文库元素。每个单元将通过数码相机提供对蠕虫行为和形态的观察和分析，并通过改变光照水平和轻微电击来奖励/惩罚某些行为。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，筛选文库中增加蠕虫运动、改变头部发育、抵消毒素影响或加快操作性条件反射学习速度的试剂)。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浮萍上，但最终版本将对许多生物有用(包括携带荧光记者的转基因生物，用于分析特定特征)。它将使筛选小分子、RNAi、蛋白质、抗体和其他库成为可能。潜在的目标包括：改善记忆，增加或减少运动活动，改变神经元生长，抵消已知药物的影响，增强或抑制感觉方式，在再生过程中改变形态，减缓衰老，加速或减慢新陈代谢，或对已知的有毒化合物起抗毒素作用。

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.