The Biochemistry Department of the University of Geneva: Understanding the Molecular Basis and Function of Intracellular Organization
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830 CHIMIA 2009, 63, No. 12 THE 450TH ANNIVERSARYOFTHE ACADÉMIE ET UNIVERSITÉ DE GENÈVE doi:10.2533/chimia.2009.830 Chimia 63 (2009) 830–834 © Schweizerische Chemische Gesellschaft The Biochemistry Department of the University of Geneva: Understanding the Molecular Basis and Function of Intracellular Organization Marcos González-Gaitán, Jean Gruenberg, Thanos Halazonetis, Ulrich K. Laemmli, Jean-Marc Matter, Howard Riezman*, Olivier Schaad, Thierry Soldati, and Reika Watanabe Abstract: The Biochemistry Department at the University of Geneva currently has four full professors, a professor emeritus, one assistant professor, two MER (Maître d’enseignement et de Recherche) and a permanent scientific collaborator. The research interests of the members of the Biochemistry Department are described. Keywords: Animal cells · Cell division · Dictyostelium · Drosophila · Endocytosis · Lipids · Organelles · Secretion · Signaling · Yeast · Zebra fish Introduction The Biochemistry Department at the University of Geneva currently has four full professors, a professor emeritus, one assistant professor, two MER (Maître d’enseignement et de Recherche) and a permanent scientific collaborator (Fig. 1). Two of the professors have joint ap- pointments with the Department of Mo- lecular Biology, Thanos Halazonetis has his laboratories in Molecular Biology and Marcos González-Gaitán has his laborato- ries in Biochemistry. The director is cho- sen yearly by consensus and is currently Howard Riezman. The department teaches informatics for chemists and biochemists, as well as biochemistry at all levels. The research in the department is highly fo- cused on membrane biology and cellular organization, however the systems used Fig. 1. Current members of the Biochemistry department at the University of Geneva (October and the questions addressed are highly di- 2009). Top row, left to right, Jean-Marc Matter, Olivier Schaad, Thierry Soldati, Marcos González- versified (Fig. 2). Most of the topics of re- Gaitán, Jean Gruenberg, Ulrich Laemmli, bottom row, left to right, Thanos Halazonetis, Reika search concern the biosynthesis, function Watanabe, Howard Riezman and trafficking of membranes. The groups of González-Gaitán, Gruenberg, Riezman has specialized in bioinformatics and has and Soldati have all worked on the path- been involved in data analysis of transcrip- way of endocytosis, especially concerning tion and lipidomics. In this short article the the roles of endocytosis in fly develop- research accomplishments of the different ment, the formation of multivesicular bod- groups are exposed. ies in animal cells, the internalization step in yeast, and phagocytosis in Dictyoste- lium discoideum, respectively. The Wata- In and Around the Nucleus nabe and Riezman groups have worked on membrane trafficking from the endoplas- Linking the regulation of gene expres- *Correspondence: Prof. H. Riezman Department of Biochemistry mic reticulum. The Laemmli group works sion to ontogenesis remains a major issue Sciences II on nuclear organization and how it regu- in developmental neurobiology. The Mat- 30 quai Ernest-Ansermet lates gene expression. The Matter group ter group is interested in defining how the CH-1211 Genève 4 works on developmental neurobiology and interplay between regulatory factors and Tel.: +41 22 379 6469 Fax: +41 22 379 6470 his laboratories are housed in the depart- key transcriptional targets coordinates the E-mail: [email protected] ment of Animal Biology. Olivier Schaad complex processes of neuron specifica- THE 450TH ANNIVERSARYOFTHE ACADÉMIE ET UNIVERSITÉ DE GENÈVE CHIMIA 2009, 63, No. 12 831 molecular genetics is one of the most highly cited studies in the history of science.[30–36] The bacteriophage work was done before Prof. Laemmli moved to Geneva. When he arrived in Geneva he devoted most of his efforts towards the study of how eukaryotic chromosomes are organized and has pub- lished numerous articles in this field in the most prestigious journals.[37–45] His work revealed the presence of a nuclear scaffold to which the DNA is attached. This creates chromosomal DNA loop structures. These structures are important features, not only to explain how the DNA is organized in the nucleus, but also how gene regulation is controlled. More recently he has shown that nuclear pores interact with the pro- moter regions of genes influencing their expression[46] and he has introduced novel technology to rapidly inactivate proteins by sequestering them away from their site of action.[47] Fig. 2. A schematic representation of the cell with the names of the groups and the cellular struc- tures on which they work. Intracellular Trafficking and Membrane Biogenesis tion and morphogenesis of the retina.[1] scription[8,9] where he made important con- Although retina development relies on the tributions before shifting his attention to The major aim of the Soldati group is whole on regulatory proteins widely ex- oncogenesis, in particular the role of DNA to understand the integration, the coopera- pressed in the developing nervous system, damage in cancer. He has become a world tion of signalling, cytoskeleton and mem- Atonal homolog 5 (Ath5) expression is a leader in this field in which he has investi- brane trafficking in phagocytosis and its specific feature of retina ontogenesis.[2] gated the mechanism whereby cells detect relevance to host–pathogen interactions. The group focuses on the regulation and and respond to DNA damage, in particu- To this end, they use the social amoeba function of Ath5 as a key determinant of lar double strand DNA breaks.[10–20] These Dictyostelium as a model organism as it the retina cell fate and as an important studies have important implications for the is a professional phagocyte very similar to regulator of neuronal patterning. They ask understanding of the origins of cancer, in mammalian phagocytes of the innate im- how Ath5 interconnects a cell fate decision particular, because DNA damage and the mune system in morphology and behav- with the genetic pathways that regulate cell way a cell deals with it seem to be early iour, but it is genetically and biochemically cycle exit, cell polarity and cell migration. predictive parameters for oncogenesis. tractable.[48] In the recent past, their work The characterization of interspecies In recent years, Olivier Schaad has fo- has concentrated on the lipidomic and differences in gene regulation is crucial cused on the analysis of microarray data. proteomic characterisation of phagosomal to understanding the molecular bases of He was concerned with the subsequent components[49] (Dieckmann and Soldati, in phenotypic diversity and evolution. Ath5 management of the huge amounts of com- press), as well as on the molecular dissec- participates in the ontogenesis of the ver- puter data, and development of software tion of the role of actin and class I myosins tebrate retina. Their study reveals how evo- to analyse microarray data.[21–29] He ap- in the formation and closure of the phago- lutionarily conserved, non-coding DNA proached the analysis of microarray data cytic cup, and in the flux of membrane sequences mediate both the conserved and in a quantitative manner starting by the during maturation and recycling from en- the species-specific transcriptional fea- developing of software for the automation dosomes/phagosomes.[50] The projects are tures of theAth5 gene.[3,4] In the mouse and the analysis of microarray data. being extended to include other major reg- chick retinas, species-related variations in A recent focus of his work has been the ulators of the specificity and efficiency of the chromatin-binding profiles of bHLH study of microarray data for the analysis of membrane transport such as the Rab GT- transcription factors correlate with distinct circadian gene expression.[25] The discov- Pases and the exocyst tethering complex. features of the Ath5 promoters and under- ery of circadian transcripts is a challeng- Crucially, the group has established lie variations in the transcriptional rates of ing task. There are two major difficulties: Dictyostelium as a model host to study the Ath5 genes.[5–7] The different expres- the lack of high temporal resolution in the infection and dissemination of pathogenic sion kinetics of Ath5 generate differences levels of expression of the transcripts of mycobacteria.[51] Interestingly, pathogenic in the expression patterns of a set of genes interest and the large number of probe- mycobacteria such as M. tuberculosis, M. regulated by Ath5 in dose-dependent man- sets (>45,000) to analyze. He developed marinum and M. leprae use common strat- ner, including those involved in neurite an automatic and robust procedure that egies to invade phagocytes of the innate im- outgrowth and growth cone migration. addresses these challenges. The algorithm mune system, manipulate their otherwise In sum, they show how highly conserved combines Fourier analysis, random permu- bactericidal phagocytic apparatus and in- regulatory elements are put to use mediat- tation, and least square optimization. crease the success of cell-to-cell transmis- ing non-conserved functions and creating Prof. Ulrich K. Laemmli has been a pio- sion. M. marinum, a fish pathogen, is the interspecies neuronal diversity (Skowron- neer in the fields of biochemistry and mo- closest relative to the tuberculosis group ska-Krawczyk et al. in press). lecular biology. His early work was on the of mycobacteria and provides a powerful Prof. Thanos D. Halazonetis began his biogenesis