Heran Darwin, PhD

My lab seeks to understand how Mycobacterium tuberculosis, the causative agent of tuberculosis, has become arguably the most successful pathogen on earth. M. tuberculosis naturally infects humans only, and one-third of the world’s population is infected by this bacillus.

Using genetics and biochemistry, my lab has characterized a protease complex called the proteasome, which is essential for M. tuberculosis to cause lethal infections in animal models. Proteasomes are a family of proteases that are conserved in all domains of life, from bacteria to humans. Over the years, we have identified proteins that function with the M. tuberculosis proteasome, several of which are unique to bacterial proteasome systems.

In addition to characterizing the mechanisms of proteasome-dependent degradation, we have identified pathways regulated by this sytem, many which are essential for the tubercle bacillus to persist in a mammalian host. We are currently employing genetics, proteomics, and metabolomics to understand these pathways.

Also of interest, over the years we have found that M. tuberculosis can harbor mutations that prevent the death of its host, yet the host’s immune system is unable to clear the infection. We are very interested in understanding how these bacilli remain in the host despite their inability to replicate robustly.