High Throughput Screening in Parkinson’s Disease

ABSTRACT

Genomic approaches provide enormous amounts of raw data with regard to genetic variation, the diversity of RNA species and protein complement. High-throughput (HT) and high-content (HC) cellular screens are ideally suited to contextualize the information gathered from other ‘omic’ approaches into networks, functional role and can be utilized for the identification of therapeutic targets. Current methods used for HT-HC screens are laborious, time consuming and prone to human error. Thus we developed an automated highthroughput system with integrated fluorescent imager for HC screens called the AI.CELLHOST. The implementation of user defined culturing and assay plate setup parameters, allows parallel operation of multiple screens in diverse mammalian cell types. We demonstrate that such a system is able to successfully maintain different cell lines in culture for extended periods of time as well as significantly increasing throughput, accuracy and reproducibility of HT and HC screens.

INTRODUCTION

High throughput screens (HTS) and high-content screens (HCS) can facilitate our understanding of the information gathered from other ‘omic’ approaches into networks and function in an appropriate time scale. Limited throughput, high cost, environmental variation and human error have led to low screen reproducibility and significant concerns about type I and II errors which have precluded HT/HC screening from delivering on its full potential of aiding genomic annotation and drug discovery. In order to manipulate and detect changes in various cellular processes in the time and scale that is necessary, new methods have to be developed. These methods have to decrease variation, error and cost, while increasing sensitivity and reproducibility. To address these issues, we developed the AI.CELLHOST. The system is a fully automated cell culture robot with an integrated fluorescent imager, which allows one to conduct HCS in a variety of cell types with increased precision and reproducibility.

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