Principal Investigator (PI)
The Foundation is providing £102,849 in support.
Monika Jankute - Sudagar Gurkha
Our aim is to conduct a phenotypic high-throughput screen of the “TB box”, a set of known M. tuberculosis inhibitors from the GSK collection. BHAM have developed a novel whole cell reporter assay for protein synthesis inhibition in mycobacteria, such as M. bovis BCG and M. tuberculosis. This assay utilises anhydrotetracycline-inducible mCherry expression that, in the presence of a dose response ribosomal inhibitors, produces a dose-dependent reduction in fluorescent output, which can be monitored by an automatic fluorimetric plate reader. This assay will provide an insight into the mode of action of hit compounds, which can be further validated biochemically and by the generation of spontaneous resistant mutants and whole genome sequencing. This work will be used to compliment a biochemical ribosomal HTS being conducted by Prof. Sacchettini´s group, wherein phenotypic hits will be validated for target engagement in the biochemical assay at Texas A&M University.