Talk Title: Quantitative interaction proteomics: Insights into biological systems
Ben is a group leader at the Institute of Molecular Systems Biology at ETH Zurich. In 2016 Ben was awarded a Swiss National Science Foundation ‘Ambizione’ grant which led to establishment of our group. Our research is focused on the development of advanced mass spectrometry-based proteomic methods, with a focus on protein-protein interactions, and their application to problems in host-pathogen biology. We have been actively developing SWATH-MS, and we have used this method to study the dynamic re-organization of protein-protein interaction networks by affinity purification coupled with with SWATH-MS in signaling systems. Current work is centered on the application of these methods to host-pathogen interactions in the clinically relevant pathogen Mycobacterium tuberculosis. Prior to this Ben completed postdoctoral work with Ruedi Aebersold at ETH Zurich, a Newman Fellowship (postdoctoral) in Quantitative Proteomics (sponsored by Agilent Techologies) at University College Dublin, and a PhD thesis at University College Dublin.
Protein complexes and protein interaction networks are essential mediators of most biological functions. Complexes supporting transient functions such as signal transduction processes are frequently subject to dynamic remodelling. Currently, the majority of studies on the composition of protein complexes are carried out by AP-MS and present a static view of the system. We have previously used AP with SWATH-MS to interrogate signaling complexes in perturbed systems (Collins et al. Nature Methods 2013). I will describe new applications of this strategy in relevant biological systems. Firstly I will show how quantitative analysis of a disease related mutant of the ubiquitin-directed AAA-ATPase p97 has led to the discovery of new substrates in addition to insights into the modularity of p97 adaptor proteins. Second, I will show that, combined with transgenic mouse technology, AP-SWATH allows to examine dynamic re-organization of signaling complexes in developing or mature primary T cells after stimulation.