ayout 1 - EMBL Grenoble

Directors’ Research
Directors’ Research is unlike other EMBL units in that it covers two thematically distinct research
groups, headed by the Director General and Associate Director of EMBL. As the DG and AD have
substantial management responsibility for all the units of EMBL, their laboratories are administratively
separated from the other units.
The Mattaj Group has studied 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 focussed on identifying the factors that
are involved in NE assembly and their modes of action. NE assembly is a multi-stage process. 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 begun to understand how Ran controls NPC assembly, but has little
information on how the NE membranes assemble, or how NPC insertion into the membranes
takes place. In addition, although it is known that Ran regulates where NE assembly occurs in the
cell, they do not know 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 an ambitious 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 work on post-transcriptional control 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 research in the
MMPU on the regulation of the iron hormone hepcidin and its involvement in iron overload and
deficiency diseases.