Directors' Research
Directors’ Research is unlike other EMBL units in that it covers three thematically distinct research groups, headed by the Director General and Associate Director of EMBL and the Director of EMBO. As the DG and AD have substantial management responsibility for all the units of EMBL, their laboratories are administratively separated from the other units.
| Mattaj Group | The RanGTPase as a spatial regulator |
| Hentze Group | Cytoplasmic gene regulation and molecular medicine |
| Leptin Group | Generation of complex cell shapes: membrane vesicles, polarity proteins and localised mRNAs |
| Karsenti Group | Planctonic ecosystems in TARA OCEANS expedition |
The Mattaj Group studies diverse processes that are under the control of the Ran GTPase. During mitosis, Ran is needed for both mitotic spindle assembly and nuclear envelope (NE) formation. Their studies have demonstrated that Ran’s mitotic functions occur by the same mechanism as nucleo-cytoplasmic transport, i.e. via regulation of interactions between transport receptors and factors involved in spindle or NE assembly. Currently they are focused on identifying the factors that are involved in NE assembly – a multi-stage process – and their modes of action. Both the membranes that give rise to the NE and the proteins that form nuclear pore complexes (NPCs), through which transport across the NE occurs, associate with the chromatin surface early in NE assembly. Membrane fusion events and NPC assembly proceed in concert, and have to be regulated in an integrated way. The group has made progress in understanding how Ran controls NPC assembly and has identified other protein and lipid kinases and phosphatases involved in regulating NE assembly. Their detailed mechanisms of action are under study. In addition, although it is known that Ran regulates where NE assembly occurs in the cell, it is not known how the process is temporally regulated, i.e. why it occurs in telophase rather than at other times during mitosis. Understanding the spatial regulation of mitotic events by Ran and their temporal regulation during the cell cycle is a long-term goal.
The Hentze Group combines interests in the post-transcriptional regulation of gene expression and in mammalian iron metabolism with research on diseases that result from disturbances in both areas. Their post-transcriptional control work mainly addresses the regulation of protein synthesis, examining the mechanisms of action of regulatory RNA-binding proteins and/ or miRNAs on the translational apparatus. In the context of the Molecular Medicine Partnership Unit (MMPU), they also investigate (jointly with Andreas Kulozik from Heidelberg University) nonsense-mediated RNA decay and 3’ end processing as aspects of mRNA metabolism that give rise to common hematological disorders. The use of mouse models has become central to their exploration of the IRE/IRP network in mammalian iron homeostasis. The group studies the importance of this regulatory network for physiological cell and organ functions as well as its involvement in human disorders. Together with Martina Muckenthaler of Heidelberg University, the group also undertakes MMPU research on the regulation of the iron hormone hepcidin and its involvement in iron overload and deficiency diseases.
The Leptin Group uses two cell types to study the processes determining cell shapes. The branched terminal cells of the Drosophila tracheal system contain an intracellular membranous tube that transports oxygen to cells. The mechanisms involved in establishing the cells’ architecture, especially the oxygen-carrying lumen, are poorly understood, and the group studies the role of vesicle trafficking and fusion, polarity protein complexes and the cytoskeleton. As subcellular localisation of mRNA and the local control of translation are recognised as significant for polarised cellular functions, the group have also developed an in vivo screening method to identify genes with asymmetrically localised RNA in tracheal cells. This has already led to the discovery of new genes which will be used to build a sequence database of mRNAs with tissue-specific polar distributions. Collaborating laboratories will use the insertion stocks to screen other cell types, resulting in a valuable bioinformatic resource. Secondly, the epithelial cells in the embryo mesoderm are used to study the dynamics of epithelial junctions during cell shape changes and epidermal-to-mesenchymal transitions, using laser microsurgery, live imaging, genetic and cell biological methods.
Eric Karsenti (Karsenti Group), who moved from Heads of the Cell Biology and Biophysics Unit to the Directors Research, works along two lines. He is continuing some work on the principles that govern the organisation of cellular components into complex patterns, as well as on the collective behaviour of cells and their organisation in complex tissues, in collaboration with Lars Hufnagel and Darren Gilmour.
However his main activity has now shifted towards the coordination of the oceanographic expedition TARA OCEANS. This expedition involves a world-wide survey of microscopic marine ecosystems from viruses to zooplankton as well as the study of specific, poorly known coral reef ecosystems. The mission of the expedition is to bring back quantitative and qualitative data on the composition of these ecosystems as a function of geographic position and environmental conditions. The goal of this collection of samples and data is 3 fold:
1) to feed morpho-genomic analyses of these populations in order to better understand the nature of the organisms and genes expressed in a given oceanic environment.
2) to better understand the evoution of marine organisms and
3) to feed dynamic ecological models of the co-evolution of these ecosystems with the hydro-climate.
In addition to coordinating the expedition, Eric Karsenti will interact with Jan Ellenberg (Ellenberg Group) at EMBL to develop high throughput imaging of protists and small metazoans, with Detlev Arendt (Arendt Group) on the biogeography and evolution of marine annelids and with Peer Bork (Bork Group) on the development of a database and genome analyses.