Research

Main content

Motivation

Cellular processes in health and disease emerge from dynamic molecular networks of enormous complexity. Proteins represent the most abundant class of cellular network components. More than 10 billion molecules of over 100000 different proteins are estimated to form into stable and transient complexes that are organized into dynamic regulatory networks that coordinate the various processes in a typical human cell. This seeming molecular complexity represents an enormous analytical challenge. Not surprisingly only a small fraction of the protein networks in human cells has been characterized to date. In our group we develop and apply new quantitative mass spectrometry approaches to systematically study the topology and temporal control of protein networks at high through put and quantitative accuracy.
We are specifically interested in dynamic networks controlling cell signaling and epigenetic gene regulation linked to human diseases. We believe that understanding the topology and temporal organization of such networks represents an important conceptual framework to better interpret and predict disease phenotypes emerging from patients’ genomes.

Approach

We develop and apply various approaches for the biochemical enrichment of protein complexes (size exclusion chromatography, affinitiy purification and biotin proximity labelling). These techniques are combined with mass spectrometry based proteomics techniques to reveal composition, stoichiometry and temporal control of protein complexes. Computational tools for visualization of proteomic data and their integration with genomic and phenomic data are used to infer new hypthesis that can be tested by specific functional experiments.

Specific projects of the group

Topology and dynamics of cell signaling networks

 

  1. Characterization the endothelin signaling system and its role for cell growth (Alex Schäfer in collaboration with ACTELION)
  2. The protein interaction landscape of the human kinome in health and disease (Audrey van Drogen, Marija Bujan, Anton Vichalkovsky, Rodolfo Ciuffa, Martin Mehnert)
  3. Signaling dynamics controling the activation of primary T cells (Simon Hauri, Etienne Caron in collaboration with Romain Roncagalli and Bernard Malissen)
  4. Topology and temporal organization of signaling complexes controlling tissue homeostasis by the human HIPPO pathway (Federico Uliana)
modular control of the co‐activator YAP1
Interaction proteome of human Hippo signaling (from Hauri et al., MSB, 2013)

Functional proteomics of epigenetic gene regulation

  1. Modulation of human histone transferase complexes in human cancer (Fabian Frommelt)
  2. Changes in chromosomal protein complexes associated with X-chromosome inactivation (Andrea Fossati in collaboration with the lab of Anton Wutz, Molecular Health Sceinces, ETH)
  3. The molecular interaction landscape of human Polycomb complexes (Simon Hauri in collaboration with Christian Beisel, BSSE Basel)
PCG complexome analysis

Polycomb group (PcG) proteins mediate gene silencing and epigenetic memory in higher eukaryotes. By systematically mapping the human PcG complexome we resolved Polycomb subcomplexes at high resolution and identify two human PRC2 and two PR- DUB complexes. Furthermore, genomic profiling reveals segregation of PRC1 and PR-DUB target genes (from Hauri et al., Cell Reports 2016).

 

 

 
 
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Sun Feb 19 09:05:17 CET 2017
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