Development of an industry standard, high-throughput translation-inhibition discovery platform for the malaria parasite

Malaria parasites continue to evolve resistance to all frontline chemotherapeutics. As such, there is an ongoing need for novel drugs, with new modes of action, to enter the development pipeline. Ideally, those entering development will have fast modes of action, have activity across the parasite’s lifecycle, and target a validated essential process within the parasite cell, ensuring drug longevity in the field. The cytoplasmic translation machinery of the Plasmodium cell, the ribosome, could be just such a target. It plays an essential role in key aspects of parasite cellular biology (across the lifecycle), facilitating the synthesis of the majority of parasite proteins. It is also well validated, having long-standing use as the target of antibiotics for bacterial infections. Here, combining expertise in ribosomal biology, including the solving of its recent structure, with industry gold standards in assay development towards drug discovery, we propose to develop a high-content translation assay that utilises the parasite’s own protein translation machinery to screen, alongside a human translation assay, for parasite-specific ribosome/translation inhibitors. Combining the development of an industry-standard screen with cellular validation, there is a hope to lay the foundations for a major program in translation-targeting drug discovery towards novel anti-malarial therapeutics.

Basic Science
Drug-based Strategies

Apr 2015 — Sep 2016

$155,587

United Kingdom