Our laboratory discovered that Spike is a lysosomal protein, reprograms lysosomes to facilitate the lysosomal egress of SARS-CoV-2 viruses, and evolves to maximize its lysosomal sorting and minimize its plasma membrane presentation exposure (doi: 10.1126/sciadv.ade5085).
1. Identify and characterize Spike’s lysosome sorting receptor. Using a combination of genetic and biochemical approaches, we will (a) identify the lysosomes sorting receptor(s) for Spike and characterize their roles in the trafficking of Spike from the ER to lysosomes, and (b) test whether they contribute to the endolysosomal route of SARS-CoV-2 infectivity.
2. Elucidate the molecular mechanisms of Spike-mediated lysosome reprogramming. Using the similar experimental approaches, we will discover how Spike’s presence in the lysosome membrane leads to lysosome clustering and a block to endosome-lysosome fusion.