Discussion

The Anti-Wolbachia consortium (A•WOL) at Liverpool School of Tropical Medicine (LSTM) has partnered with the Global High Throughput Screening (HTS) Centre at AstraZeneca in the first open access HTS project for the World Intellectual Property Organization’s (WIPO) Re:Search program against Neglected Tropical Diseases. The A•WOL consortium aims to identify novel macrofilaricidal drugs targeting the essential bacterial symbiont (Wolbachia) of the filarial nematodes causing onchocerciasis and lymphatic filariasis. We will present the story of the assay scale-up from the original LSTM assay to a fully automated imaging assay, built to enable screening of the full AstraZeneca compound library.

The development of a higher throughput screen at AstraZeneca has dramatically evolved the original assay protocol through the optimisation of the cell culture, target-staining, plate-washing and detection technologies, along with the data analysis methods employed. The complexity of the assay protocol running at the level of throughput required meant that a complex automation regime was required. We will further describe the combination of flexible automation platforms and manual screening involved in the overall workflow-plan, in order to deliver data at a high throughput. We would propose that the hybrid model of manual workstation and flexible, modular automation is the most appropriate way to achieve the throughput needed, whilst maintaining correct incubation timings in critical points of the assay process.