High-throughput analysis of protein dynamics
Protein dynamics can be thought of as a chain of events that cellular proteins undergo from the moment of biosynthesis and until elimination. Examples of such events are synthesis on ribosomes, protein folding, interaction with other proteins, proteasomal degradation etc... In spite of the paramount importance protein dynamics is a highly understudied topic. For example, the assembly pathways (the way proteins interact with one another to form complexes) are known only for a handful of ~4000 human protein complexes. This project focuses on the development of tools to explore dynamics of cellular protein complexes.

Our approach is based on interpreting the temporal changes in cellular protein complexes as the flow of metabolic chemical reactions except that the "metabolites" are not small molecules but protein assemblies. Based on this concept we have developed an approach entitled kinetic analysis of incorporation rates in macromolecular assemblies (KARMA) that uses isotope metabolic labelling and quantitative mass spectrometry to analyse in vivo dynamics of protein complexes. This project amis at extending this approach beyond endogenous protein complexes e.g. to allow analysis of host-pathogen interactions or dynamics of other kinds of biomolecules.
Contributions:
Project design: Evgeny Onishchenko (University of Bergen)
Biochemistry: Evgeny Onishchenko (University of Bergen)
Mass spectrometry: Ludovic Gillet (ETHZ/Picotti lab); Evgeny Onishchenko (University of Bergen)
Mathematical modelling: Elad Noor (Weizmann Institute/Milo lab)
Microscopy & genetics: Jonas Fischer (ETHZ/Weis lab)
Image analysis: Pascal Vallotton (Roche AG); Jonas Fischer (ETHZ/Weis lab)
Visualisation: Jonas Fisher (ETHZ/Weis lab); Matthias Wojtynek (ETHZ/Weis lab); Olga Posukh (Institute of Molecular and Cell Biology, Novosibirsk)
Funding and research environment: Karsten Weis (ETHZ); Evgeny Onishchenko (University of Bergen)
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