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 to tackle protein dynamics is based on the idea that biogenesis of protein complexes can be seen as a flow of metabolic reactions except that the "metabolites" are not typical small molecules but cellular proteins and their assemblies. Based on this idea we have recently developed an approach entitled kinetic analysis of incorporation rates in macromolecular assemblies (KARMA) that utilises a combination of isotope metabolic labelling and quantitative mass spectrometry to dissect in vivo dynamics of protein complexes. This project amis at development of the analytical techniques to address protein dynamics of various cellular protein complexes, host-pathogen interactions or other kinds of biomolecules.