OPENDD: Open Synthetic Biology to accelerate drug discovery against tuberculosis

People involved:
Jake Wintermute
Nadine Bongaerts

Project webpage: link

Keywords: Tuberculosis, Drug Discovery, Synthetic Biology

Project description

The need for new antibiotics to combat emerging resistance is widely acknowledged. Commercial biotech companies, traditional leaders in drug development, are increasingly leaving the field as technically difficult and unprofitable. Public efforts must therefore take up the responsibility and interdisciplinary open-science collaborations must be scaled up to match the global challenge.

Here we propose a synthetic biology platform for targeted drug screening with the potential to scale to assay hundreds of metabolic drug targets in dozens of human pathogens. We will construct Target-Essential Surrogate E. coli (TESEC) strains, in which an essential metabolic pathway has been deleted and replaced with a pathogen-derived equivalent pathway. Agents that inhibit the growth of TESEC strains, but not wild-type controls, must inhibit the activity, expression or maturation of the targeted pathway.
Publication and deliverables

Atanaskovic, I., Bencherif, A.C., Deyell, M., Jaramillo-Riveri, S., Benony, M., Bernheim, A.G., Libis, V.K., Koutsoubelis, N., Zegman, Y., Löchner, A.C. and Basier, C., 2014. In Situ characterization of mycobacterial growth inhibition by Lytic Enzymes expressed in Vectorized E. coli. ACS synthetic biology, 3(12), pp.932-934. (pdf)