The problem of persisting dormant cells is especially acute in the case of tuberculosis – every third person is a non-symptomatic carrier of a “latent” form. This latent form, which we think are persister cells, then wakes up causing an active disease.
With support from The Gates Foundation, we are studying the mechanism of persister formation in M. tuberculosis. The focus is on isolating persisters from in vitro grown cultures and also from infected macrophages and mice and obtaining their transcriptome in search of persister genes. Another approach we are using is to analyze high-persister mutants by whole genome sequencing, in collaboration with scientists from The Broad Institute.
Apart from basic science, we participate in discovering new anti-TB drugs. One approach is to find sterilizing compounds acting against persisters using synthetic compound libraries; and another involves screening of extracts from previously uncultured bacteria. The drug discovery project is a collaboration with NovoBiotic.