ayout 1 - EMBL Grenoble

EMBL Research at a Glance 2009
Anne-Claude
Gavin
PhD 1992, University of
Geneva.
Postdoctoral research at EMBL.
Biochemical and chemical approaches to
biomolecular networks
Previous and current research
How is biological matter organised? Can the protein and chemical worlds be matched to understand
the cell’s inner works? As our knowledge about the basic building blocks of eukaryotic
genomes, proteomes and metabolomes grows, the challenge remains to understand how these
parts relate to each other. At cellular levels, gene products very rarely act alone; the orchestration
of complex biological functions is the result of networks of molecules. Traditional approaches have
typically focussed on a few, selected gene products and their interactions in a particular physiological
context. We are proponents and pioneers of more general strategies aiming at understanding
complex biological systems, and follow three main lines of research to understand the
principles that govern the assembly of these networks.
Director, Molecular and Cell
The charting of protein-protein interaction networks: Our knowledge of protein-protein interaction
is still anecdotal; current estimations reveal that probably less than 10% have been charac-
Biology, Cellzome AG,
Heidelberg.
terised so far. We adopted tandem-affinity purification/mass spectrometry (TAP/MS) technology
Group leader at EMBL since
2005.
to perform a genome-wide analysis of protein complexes in the yeast S. cerevisiae. More than 400
different protein complexes, more than half entirely novel, were characterised. The approach was
particularly successful in further extensive collaborations within the programme, which aimed
the structural characterisation of protein complexes through integration of electron microscopy data and in silico approximations.
The study of protein complexes and network order of assembly and dynamics: Generally, the use of protein interaction networks to predict
the behaviour of whole systems has been relatively limited. Protein networks usually fail to capture the dynamic aspect of protein interactions
that is essential for the functioning of the whole cell. The charting and modelling of the highly dynamic assembly and reorganisation
of protein complexes following cell perturbation represents one of the major current research interests of the group.
The extension of interaction networks from proteins to other cell’s building blocks; metabolites-on-proteomes networks: Metabolites account
for about half of the cell’s volume and represent important class of biomolecules. They have long been considered simple building blocks
for the assembly of more complex macromolecules. It is however becoming evident that the interactions between the metabolites’ and the proteins’
worlds are not limited to substrate/product relationships. Metabolites can have well known signalling functions and many proteins are
allosterically modulated by metabolites. These bindings are sometimes mediated by a variety of specialised domains. Every time it has been possible
to chart such interactions they turned out to have profound functional implications.
The interactions taking place between the cell’s chemical world and proteomes are
still poorly defined and have certainly not yet been studied in a comprehensive way;
this represents the second major research interest of the group.
Future projects and goals
• Analysis of the order of assembly and dynamic nature of yeast protein complexes,
in a pathway oriented approach.
• Further development and improvement of existing chemical biology methods,
based on affinity purification (‘metabolite pull-down’) to monitor protein-metabolites
interaction.
• Global screen aiming at the systematic charting of the interactions between
the proteome and the metabolome in Saccharomyces cerevisiae.
• Develop new and existing collaborations with computational and structural
biology groups at EMBL and outside to tackle the structural and functional
aspects of biomolecular recognition.
Graphic: Petra Riedinger
Selected references
Charbonnier, S., Gallego, O. & Gavin, A.C. (2008). The social network
of a cell: Recent advances in interactome mapping. Biotechnol.
Annu. Rev., 1, 1-28
Kuhner, S. & Gavin, A.C. (2007). Towards quantitative analysis of
proteome dynamics. Nat. Biotechnol., 25, 298-300
6
Gavin, A.C., Aloy, P., Grandi, P., Krause, R., Boesche, M. et al.
(2006). Proteome survey reveals modularity of the yeast cell
machinery. Nature, 0, 631-636
Aloy, P., Böttcher, B., Ceulemans, H., Leutwein, C., Mellwig, C.,
Fischer, S., Gavin, A.C., Bork, P., Superti-Furga, G., Serrano, L. &
Russell, R.B. (200). Structure-based assembly of protein complexes
in yeast. Science, 303, 2026-2029