Speaker: Alex Paredez, University of Washington professor in the Department of Biology

Title: "Unexpected evidence of autophagy in Giardia"

Abstract: Giardia has a simple endomembrane trafficking system that lacks conventional endosomes and lysosomes. The genome is missing most autophagy (ATG) genes so bioinformatic studies suggested that Giardia is unlikely to have an intact autophagy pathway. Through our studies of encystation we discovered that Giardia induces the formation acidic compartments that are distinct from the known hybrid endosome/lysosome like peripheral vacuoles (PVs). These compartments are marked by Giardia’s sole Rho family GTPase GlRac and we found that the induction of encystation results in acidic compartments in up to 30% of cells compared to 10% in non-encysting cells. Additionally, starvation induces the formation of these compartments in up to 91% of cells. Transmission electron microscopy has confirmed that these compartments are surrounded by a double membrane, consistent with classic autophagosomes. Actin has a role in autophagosome formation in both plants and animals. A new live Actin-Halo marker indicates that Actin is recruited to autophagic structures. The induction of autophagy during encystation and starvation is consistent with autophagy being important for cell remodelling during differentiation and resource scavenging during starvation. Quinacrine, a known inhibitor of autophagy is currently used to treat metronidazole resistant Giardia, but the mechanism of action in is unclear. Here we show that quinacrine is concentrated in this newly discovered compartment. The identification of autophagosomes and Giardia’s sensitivity to quinacrine suggests autophagy could be a rich source of new therapeutic targets. Additionally, the recruitment of actin to autophagosomes could be used to identify how actin dynamics are regulated in Giardia which lacks all canonical ABPs.

Host: Moe Gupta, associate professor in genetics, development and cell biology