University of Sydney

Start : August 2014 | Status : Complete

The scientist: Dr Jessica Baiget will focus the research on the discovery of new drugs for Mycobacterium tuberculosis infection through a project titled "An Open Source Hit-to-Lead Campaign in Tuberculosis Drug Discovery”. Jessica is an experienced researcher who will drive this project under guidance of Associate Professor Matthew Todd, currently involved with the Australian Research Council/MMV-funded Open Source Malaria project, which involves hit-to-lead and lead optimization campaigns in the public domain.

The sponsors:  The University of Sydney, founded in 1850, is Australia’s first university and has built a solid international reputation for itself over the past 150 years. It is considered one of Australia’s leading educational institutions, playing a key role as a member of both the Group of Eight and the Association of Pacific Rim Universities (APRU).

Foundation funding: The Foundation is providing £67,000 in support.

GSK’s contribution: GSK is providing in-kind contributions including biological evaluation, facilities and expertise from supporting scientists.

Project Description: Mycobacterium tuberculosis (TB) is a human pathogen that infects up to one-third of the global population and causes one of the most recalcitrant bacterial infections of the modern era. Current drug discovery efforts toward TB are significant, but are taking place in a challenging environment.
Collaborations to improve research efficiency are frequently limited, preventing those with high levels of expertise from participating. Many research projects do not share negative data, preventing the formation of an effective scientific model. Many existing chemical compounds worldwide are not evaluated in medicinal chemistry campaigns because the owners of those compounds are unaware of the compounds’ potential.

This project employs a fully open source approach using public domain GSK compounds active against TB as the starting point. All data and ideas are freely shared. A TB hit-to-lead campaign will be pursued, with the intention of developing sufficient preliminary data for major future grant funding beyond the Tres Cantos Open Lab Foundation award.
Associate Professor Todd recently demonstrated the idea of open source science in the synthesis of the anthelmintic praziquantel as a single enantiomer. More recently he has applied the same ideas in drug discovery with the Medicines for Malaria Venture founding the Open Source Malaria consortium. More than 200 new public domain compounds have been synthesized and nanomolar hits have been evaluated in vivo. The open nature of the project has stimulated intellectual and practical contributions from scientists outside the core team. This state of the art will be combined with GSK’s open TB data to develop an open source project in TB, but with additional components that will overcome limitations of the open source model identified to date, such as the ability to acquire archived compounds not listed in commercial or academic databases.