Abstract

High-Content Imaging Approaches For Drug Discovery For Neglected Tropical Diseases

Manu De Rycker, Team Leader, University of Dundee

Diseases caused by the protozoan parasites Leishmania donovani and Trypanosoma cruzi cause significant morbidity and mortality in the developing world. Current treatments are inadequate and there is an urgent need to develop new drugs. In the Drug Discovery Unit at the University of Dundee we run a large programme aimed at discovering and developing new drugs for these diseases. A major challenge from a hit-discovery point-of-view is that the parasites are intracellular for a large part of their human life-cycle stage, which significantly increases the complexity of the in vitro assays. We have developed high-content imaging assays for both L. donovani and T. cruzi with a throughput suitable for hit-discovery purposes. In addition we have set up a panel of secondary assays, many also imaged-based, for further characterisation of the primary hits. Together the assays form a screening cascade designed to combine high-throughput and robustness with in vivo predictivity. The adoption of automated image-based screening technologies has had a significant impact on our ability to carry out drug discovery for neglected tropical diseases and has resulted in the development of drug pipelines for both visceral leishmaniasis and Chagas disease.