Cell Biology, Biophysics, Multifunctional proteins, iron metabolism, high resolution imaging.
Dr. Raje’s work on maintenance of iron homeostasis has overturned the six decade paradigm of iron acquisition and release by cells. In the process his laboratory has been the first in the world to introduce the concept of Higher Order Moonlighting Behavior in biological macromolecules a novel concept in the molecular management strategies utilized by living organisms. These findings are the key to understand the balance of host pathogen interactions in tuberculosis by identifying conserved pathogen proteins essential for virulence. Due to their homology with human proteins, these remain undetected and hijack host mechanisms to appropriate critical resources and enhance infection. Iron acquisition is central to the survival of invading M.tuberculosis. A key discovery from Dr. Raje’s laboratory was that M.tb, presents several evolutionarily conserved proteins on its surface where they moonlight as receptors for mammalian iron carrier proteins. He discovered that one such molecule Glyceraldehyde-3-phosphate-dehydrogenase can internalize mammalian iron carriers into M.tb cells. This provided a completely new perspective not only in terms of mycobacterieal iron acquisition, but also revealed the occurrence of receptor-mediated uptake and trafficking of macromolecules into bacilli a phenomena that has never previously been reported in M.tb. These findings are the key to understand the balance of host pathogen interactions in tuberculosis.