Marie-Christine Dabauvalle (EM)

Marie-Christine Dabauvalle is a cell biologist with special interest in the function and dynamics of the nuclear envelope. She graduated from the University Paris 7 (France), where she also obtained her PhD in 1979 for a thesis performed at the cancer research institute “Gustave Roussy” in Villejuif (France). Then Marie-Christine spent several years as postdoc at the German Cancer Research Center in Heidelberg (until 1985, with Werner W. Franke), where she studied the transmembrane exchange of macromolecules through the nuclear pore complexes. During this time she was habilitated by the University Paris 7 (1984). After that she joined Eric Karsenti´s group at the EMBL in Heidelberg and studied the structure and duplication of centrosomes (1985-1987). In 1987 she moved as lecturer to the University of Würzburg and since 1994 she is associate professor at the Division of Electron Microcopy (apl. Professorin since 1998). Her research concentrates on mechanisms involved in the formation of nuclear pore complexes and the impact of the nuclear envelope and nuclear membrane-associated proteins on various forms of muscle dystrophies. Furthermore, Marie-Christine is head of the Gender Equality office of the University.

In eukaryotic cells, the nucleus is surrounded by the nuclear envelope which is penetrated by nuclear pore complexes (NPC) to allow for the exchange of macromolecules between nucleus and cytoplasm. These bidirectional transport processes are highly selective, saturable and energy-requiring. Knowledge of NPC structure, composition and molecular organization is a necessary prerequisite to understanding these transport mechanisms. Marie-Christine Dabauvalle is studying structural and functional aspects of NPCs using Xenopus laevis as model organism. Her group could show that nuclear actin is critically involved in the NPC-mediated nuclear export of proteins with leucine-rich nuclear export signals. NPCs are dynamic structures. During mitosis the nuclear envelope breaks down into numerous vesicles and reforms at telophase. A particular suitable system to analyze specific events involved in nuclear envelope assembly is provided by the cell-free system based on Xenopus egg extract. The group of Marie-Christine Dabauvalle demonstrated for the first time that annulate lamellae (pore complex-containing membrane cisternae) assemble spontaneously in such extracts to which no chromatin has been added. Based on these results it was possible to separate experimentally two important processes involved in nuclear envelope assembly: formation of the double-layered nuclear membrane (resulting in NPC-free nuclei) and insertion of NPCs into the membrane. They identified the Major Vault Protein (MVP) as the factor which triggers the NPC assembly in a preformed double-layered nuclear membrane. Currently the group of Marie-Christine Dabauvalle is analyzing in more detail the surprising role of vaults by using a combination of biochemistry, electron microscopy and high resolution fluorescence microscopy in living cells. The “laminopathies” are a rapidly expanding group of human hereditary diseases. They are caused by mutations of proteins of the nuclear envelope, in particular of the nuclear lamina which lines and stabilizes the inner nuclear membrane. Although the nuclear lamina is a structure common to all cell types, the clinical syndromes associated with laminopathies are generally restricted to specific tissues. Patient cells of the affected tissues display profound changes of nuclear architecture and chromatin organization. A second focus of the current work of Marie-Christine Dabauvalle is to explore the relationships between nuclear lamina dysfunction and muscular dystrophy.