Periodic Reporting for period 1 - CR-PHAGOCYTOSIS (Complement-mediated phagocytosis in neutrophils)
Reporting period: 2015-04-01 to 2017-03-31
Furthermore, we have demonstrated the broad applicability of our tools, which can be used to study various physiological processes in which complement plays a role. Specifically, we used opsonized beads to study the role of complement inhibitors on surface-specific complement convertase enzymes. These studies have guided the discovery of new complement inhibitors, which can serve as a foundation for new therapeutics.
We have also used opsonized beads (and complement receptor cell lines) to evaluate the dynamics of opsonin cleavage in the presence of whole blood, which is critical in understanding how opsonins direct the effector functions of complement in a physiological context. In addition, we have used opsonized beads and bacteria to investigate the role of opsonins in driving complement-mediated adaptive immunity. Using this information, we can “direct” complement opsonization on bacterial surfaces to efficiently evoke the desired response (i.e. adaptive immune response, bacterial killing, etc.). This is a promising strategy in combating the rise in antibiotic-resistant bacterial infections.
Overall, the work from this project provides the tools to study a wide variety of complement-dependent processes at a molecular level, guides the development of therapeutic molecules against highly-specific active targets of the complement cascade, and provides strategies for improved cancer immunotherapies and treatment of antibiotic-resistant bacterial infections.