Pradeep Sathya

Pore forming toxins (PFTs) belong to a class of bacterial exotoxins that disrupt the biological membrane barrier by formation of nanopores which cause cellular ion imbalance. These toxins are central to the virulence of pathogens that cause diseases such as cholera, anthrax and pneumonia. Unique to this class of proteins is their ability to exist in bi-stable states i.e. they are produced in soluble forms and upon exposure to membrane, undergo conformational changes, oligomerization and form a stable membrane integrated structure. We are trying to understand the mechanism of toxin assembly by a combination of biochemical techniques, single-molecule fluorescence, fluorescence correlation spectroscopy and molecular dynamics  simulation. Towards this, we have identified novel means of regulation of toxin function which involve both binding mediated stabilization of conformation as well as allosteric regulation of channel function by distal protein segments.