CPB Seminar - Marcus Taylor
14 July (in person)
Marcus Taylor
(Max Planck Institute for Infection Biology, Berlin)
Higher-order oligomeric assembly in the innate immune system: Myddosome assembly and the induction of inflammation
The Myddosome is a specialized innate immune signaling complex that activates NF-kB signaling. Critical to NF-kB activation is the formation of lysine-63 and methionine-1 linked polyubiquitin chains. How does the Myddosome control the formation of these two distinct polyubiquitin chains to activate NF-kB signaling? In this talk, I will describe how we have discovered that Myddosomes are plasma membrane-tethered organelles that concentrate and activate the protein machinery that assembles K63/M1 polyubiquitin chains. We discovered that the spatial reorganization of Myddosomes into clusters regulates the formation of M1/K63 ubiquitin chains and the activation of NF-kB signaling. Inhibiting Myddosome clustering reduced the recruitment of the K63 ubiquitin ligases TRAF6 and the M1 ubiquitin ligase HOIL1. Finally, I will describe our efforts to create a spatial and temporal map of the IL-1-Myddosome signaling network. These efforts seek to understand how extracellular signalling triggers the assembly of the Myddosome and how the stoichiometric composition of oligomeric signaling complexes remodels in time.
14 July | 10 am | Sainsbury Lab Auditorium