HCS-high content screening High content screening (HCS) refers to simple cell biological assays that can be automated into the thousands to screen a  library of small chemical compounds.   This automation is carried out by robotic liquid handlers and a robotic microscope, tied to powerful recognition software that allows the computer to learn how to select images for compound effects. McMaster has one of the first high throughput screening (HTS) facilities in academia in the world. this facility has accumulated tens of thousands of chemicals in libraries for the purpose of HTS and HCS. One example of a recent HCS was to find small molecules that either released huntingtin from the ER, or retained huntingtin at the ER. This was accomplished by imaging a stable cell line expressing huntingtin’s ER- targeting signal fused to eYFP, then applying  a concentration range of kinase inhibitors to several plates. the next result was the identification of five compounds that released huntingtin from the ER, and five that retained huntingtin at the ER. These compounds then form the basis to study endogenous full-length huntingtin back in cell biological experiments and biochemical experiments. This approach is defined as Chemical Biology. McMaster has developed one of the first Chemical Biology graduate training programs in the world.  From left to right, typical examples of HCS images: no effect, inhibition of ER targeting, and promoting ER-targeting.