To completely understand complex biological processes such as development, aging, and disease, analysis of the proteome – all the expressed proteins - is becoming increasingly important. Having the complete sequence of a genome is a necessary prerequisite for proteomics, but the DNA sequence itself does not reveal which proteins are actually expressed and active in a cell or an organism. Furthermore, in contrast to the genome, the proteome is actively changing under different biological conditions. Thus, analysis of the proteome is a key approach to better understand dynamic biological processes.
The nematode C. elegans is an important model organism because many human disease-related genes have homologues in the worm. The overall aim of our project was to systematically analyse the proteome of C. elegans using mass spectrometry. We used high-throughput approaches to determine the identity and relative abundance of more than half of all predicted proteins in C. elegans. We will use this information to gain knowledge about global regulatory patterns of gene expression. Our data are publicly available in PeptideAtlas, and we will also port all our unambiguous peptide data into WormBase, the central C. elegans repository.

Through the support of this project, the Gebert Rüf Stiftung strengthened the position of Switzerland in the growing and important fields of proteomics and systems biology. Large-scale proteomics projects require equipment and expertise that are not readily available to the normal modern biomedical research team. On the other hand, the information generated by such large-scale projects can be used by a wide range of groups. Our project has thus a strong public service component. By making our data immediately accessible both on the widely used C. elegans web site WormBase and on more detailed, dedicated proteomics web sites, we allow other groups to use our data for their own studies, thereby accelerating their own research.

For a complete understanding of the inner workings of a cell, scientists need to account for all of the thousands of different proteins it contains. Proteins constitute the active players that execute the genetic programme of a cell, and their levels and interactions are precisely tuned and controlled. To routinely monitor proteins by the thousands is difficult, since they can be present at vastly different abundances, come in various sizes and shapes, and have a more complex alphabet than just the four letters of the genome itself. In our study, we used extensive mass spectrometry measurements to overcome many of these problems and to characterize the proteins of a popular model organism, C. elegans (roundworm). Together with previous data from D. melanogaster (the fruit fly), this gives us the first opportunity to globally compare the protein levels of two animals. Surprisingly, we found that protein abundance varied very little between the two species. Thus, even though worms and flies look very different anatomically, they need similar amounts of each type of protein. Because many roundworm and fruit fly proteins also have counterparts in humans, our results suggest that similar rules will apply to our own proteins. This project sparked our interest in how proteins and their modifications change over evolutionary times, and how these changes relate to changes in the organism’s genome.

Comparative functional analysis of the Caenorhabditis elegans and Drosophila melanogaster proteomes, Sabine P. Schrimpf, Manuel Weiss, Lukas Reiter, Christian H. Ahrens, Marko Jovanovic, Johan Malmström, Erich Brunner, Sonali Mohanty, Martin J. Lercher, Peter E. Hunziker, Ruedi Aebersold, Christian von Mering, and Michael O. Hengartner accepted for publication in PLoS Biology
Comparative analysis of protein phosphorylation reveals evolutionary conserved disease networks, Chris Tan Soon Heng, Bernd Bodenmiller, Adrian Pasculescu, Marko Jovanovic, Michael Hengartner, Claus Jørgensen, Gary D. Bader, Ruedi Aebersold, Tony Pawson, and Rune Linding
submitted
PhosphoPep-a database of protein phosphorylation sites in model organisms. Bodenmiller B, Campbell D, Gerrits B, Lam H, Jovanovic M, Picotti P, Schlapbach R, Aebersold R, Nat Biotechnol. 2008 Dec;26(12):1339-40.