The Tapper membrane−traffic laboratory explores host responses, in particular the molecular mechanisms determining phagocyte membrane traffic, and how these relate to bacterial pathogenesis. 

New approaches to phagocyte membrane traffic research

Pontus Nordenfelt and Per Lönnbro planning their presentations
at the recent ESCI meeting in Uppsala, Sweden

Professional phagocytes, e.g. macrophages and neutrophils, destroy bacteria by enclosing them in a vacuole that matures to form a bactericidal phagosome. Many pathogens prevent this maturation process by interfering with intracellular signals that regulate membrane traffic. We have characterized localized secretory and pinocytic responses that occur during phagocytosis. We have also shown that pathogenic S. pyogenes bacteria can inhibit these processes and survive inside phagosomes. Our aim is to understand the molecular mechanisms involved.

To characterize the modulation of membrane traffic by intracellular pathogens, we set up a novel method to isolate phagosomes. When automated, our magnetic approach to phagosome isolation will allow high-throughput and high-resolution studies of the molecular details of intracellular survival strategies of several important human pathogens. Using the method, we will investigate the role of membrane raft-associated proteins in phagosome signaling and biogenesis. Also, we will study when, how, and if an interaction of the endoplasmic reticulum with phagosomes can occur.

Overall, our goal is to create better tools for the characterization of interactions between host and bacterial components both with respect to localization, molecular structure, and pathways of signaling involved. The present research activities extend our previous work on the regulation of phagocyte membrane traffic, now with a major focus on the maturing phagosome.