Presentations by Scotty Takashi Nishioka and Anne Marie Crooke
Scotty Takashi Nishioka presents:
Group A Streptococcus permeabilizes the phagolysosomal membrane and induces cathepsin release via SLO secretion in THP-1 macrophages
Group A Streptococcus (GAS) is a gram-positive bacterial pathogen responsible for approximately 750 million human-specific infections worldwide every year, ranging in severity from mild pharyngitis to necrotizing fasciitis, which illustrates that GAS has evolved several mechanisms to counter the innate immune response. To defend against invasive pathogens, such as GAS, the innate immune system typically deploys macrophages to phagocytose and eradicate the pathogen via engulfment into the phagosome, fusion with lysosomes, phagolysosomal acidification, and activation of proteolytic enzymes. We have previously demonstrated that GAS persists within macrophages despite trafficking normally through the phagocytic pathway. However, because GAS is not capable of surviving highly acidic conditions, this suggests that GAS instead prevents lysosomal acidification. Here, we investigated the possibility that GAS prevents acidification by physically rupturing the phagolysosomal membrane, inhibiting generation of the acidic environment necessary for activation of proteolytic enzymes.
Anne Marie Crooke presents:
Photoredox-catalyzed alkene hydroalkylation and dialkylation
Photoredox catalysis is a powerful avenue of synthetic research for the development of new carbon-carbon bond forming reactions. Using visible-light photoredox catalysis allows for access to reactive intermediates under mild conditions. We have developed a method for the generation of 1,3-dicarbonyl radicals from β-keto esters via photocatalyzed single electron transfer (SET) oxidation of an enolate intermediate. These dicarbonyl radicals undergo intramolecular addition to alkenes, followed by reduction by hydrogen atom transfer or by intermolecular coupling to styrenes. In a single step, successive intra- and intermolecular radical-alkene coupling gives access to stereochemically rich structures with two new carbon-carbon bonds and up to three stereocenters.