Federal Grant Award Summary

The University of Washington received a $485,375 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded April 1, 2026, with a completion date of March 31, 2028. This biomedical research project investigates complement-mediated clearance mechanisms of extracellular mitochondria released by dying neutrophils, with the goal of understanding how neutrophils proteolytically opsonize mitochondria with complement C3b to facilitate their removal while limiting inflammation and tissue damage. The research outputs include characterization of complement C3 release and proteolytic cleavage mechanisms in neutrophil samples from 40 patients and 20 controls through quantitative polymerase chain reaction (qPCR), flow cytometry, mass spectrometry, and immunoprecipitation analyses, as well as identification of C3-cleaving proteases using selective protease inhibitors.

The second component of this research delivers in vitro and in vivo experimental results examining the role of complement C3 in mitochondrial clearance. In vitro deliverables assess how C3 opsonization affects myeloid cell uptake, inflammatory cytokine induction, and neutrophil extracellular trap (NET) formation. In vivo studies utilizing green fluorescent protein (GFP)-tagged mitochondria injected into wild-type or C3-knockout mice will generate confocal microscopy data on mitochondrial biodistribution over time. Research is performed at the University of Washington's Seattle, Washington location under the Office of Sponsored Programs.