Matthias Trost
Proteomics to study innate immunity in macrophages
Macrophages are phagocytic cells that show a high degree of diversity and plasticity that enable them to adapt to different environmental cues. Different activation states and stimuli prepare macrophages for the uptake and processing of phagocytic preys that they will encounter depending on the environment, in which they will have to perform homeostatic, inflammatory or anti-inflammatory roles. A key organelle in this process is the phagosome, a membranous organelle formed de novo around the phagocytosed particle that fuses with a number of intracellular organelles such as endosomes and the lysosome in a process called phagosome maturation.
We performed a comprehensive proteomics characterisation of the macrophage total cell proteomes and phagosome proteomes from six well defined activation states with ~10,000 proteins quantified in cell lysates and >2000 proteins in phagosomes. We identified a substantial regulation of ubiquitylation on the phagosome which led us to characterise the ubiquitylome in response to pro-inflammatory (M1) and anti-inflammatory (M2) stimuli. Our data shows that ubiquitylation on phagosomes serves for protein recruitment and regulates both innate immune signalling functions and vesicle trafficking in inflammatory and anti-inflammatory conditions. I will outline the consequences of phagosomal ubiquitylation on two examples: 1. The role of the E3 ligase RNF115 regulating phagosome maturation in interferon-activated macrophages and 2. A novel ubiquitin-based signalling pathway downstream of macrophages scavenger receptor MSR1 and its role in obesity induced inflammation.
Biography
Matthias Trost studied chemistry in Freiburg, Germany and Manchester, UK. He received a Ph.D. in 2004 from the Helmholtz Centre for Infection Research, Braunschweig, Germany, for research on the proteome of the human pathogen Listeria monocytogenes and Listeria infected host cells. Matthias then carried out postdoctoral research with Michel Desjardins and Pierre Thibault at the University of Montreal, Canada, working on the proteome and phospho-proteome of the phagosome.
In 2010, Matthias became Programme Leader and Head of Proteomics in the MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee, Scotland, UK. Since 2017 he is Professor of Proteomics in the Faculty of Medical Sciences at Newcastle University, UK. His research focusses on developing proteomics tools in the phosphorylation and ubiquitylation area. He applies these technologies to understand signalling events in innate immunity, phagosome biogenesis and human disease and translates findings towards drug discovery using high-throughput mass spectrometry.
