CELL DIVISION IN VITRO AND IN VIVO
Prof. Dr. Andrea Musacchio
since 2011: Director, Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Phyisiology, Dortmund, Germany
1999-2010: Group Leader at the European Institute of Oncology, Milan, Italy
1995-1998: Postdoc at the Harvard Medical School, Boston
1991-1995: PhD, European Molecular Biology Laboratory and University of Heidelberg, Germany
1990: Degree in Biology from Tor Vergata University of Rome, Italy
Cells are the universal element of biological matter, and their division is of outmost importance for organismal development and for the propagation of life across generations. The reductional division of cells, known as meiosis, gives rise to gametes, whose encounter restores the genetic content (ploidy) of organisms. The equational division of cells, known as mitosis, provides the daughter cells with faithful copies of the genome. Both process are accurate and closely regulated. Our laboratory studies the molecular mechanisms of cell division, their regulation, and their deregulation in the most common disease of cell division, cancerous transformation. In particular, we focus on chromosome segregation and its regulation. Chromosome segregation to the daughter cells requires their prior capture by a microtubule-based structure known as the spindle. Chromosome capture starts in prometaphase and continues until all chromosomes have aligned at the metaphase plate, and it engages a structure on chromosomes known as the kinetochore. Kinetochores, which assemble on specialized centromeric chromatin, contain a large number of different proteins (>100 in humans), each in multiple copies. Our work focuses on the reconstitution and characterization of kinetochore function, using a variety of approaches ranging from structural to cell biology via detailed biochemical analysis. Our efforts have the potential to reveal the essence of crucial mechanisms that drive chromosome segregation in all eukaryotic cells. In the future, we envision our reconstituted kinetochores to become incorporated in “synthetic cells” created in the laboratory and capable of self-propagation in vitro.
Biochemical reconstitution of protein complexes, biophysical analysis of macromolecules (e.g. calorimetry, ultracentrifugation), X-ray crystallography, electron microscopy (EM), advanced light microscopy, cell biology. We are proficient in a number of approaches of recombinant protein production (e.g. bacteria, insect cells).
Basilico F, Maffini S, Weir JR, Prumbaum D, Rojas AM, Zimniak T, De Antoni A, Jeganathan S, Voss B, van Gerwen S, Krenn V, Massimiliano L, Valencia A, Vetter IR, Herzog F, Raunser S, Pasqualato S & Musacchio A. elife 2014, 3:e02978.
Krenn V, Overlack K, Primorac I, van Gerwen S & Musacchio A. KI motifs of human Knl1 enhance assembly of comprehensive spindle checkpoint complexes around MELT repeats. Curr Biol 2014, 24(1), 29-39.
Petrovic A, Mosalaganti S, Keller J, Mattiuzzo M, Overlack K, Krenn V, De Antoni A, Wohlgemuth S, Cecatiello V, Pasqualato S, Raunser S & Musacchio A. Modular Assembly of RWD Domains on the Mis12 Complex Underlies Outer Kinetochore Organization. Mol Cell 2014, 53, 591-605.
Overlack K, Krenn V & Musacchio A. When Mad met Bub. EMBO Rep 2014, 15, 326-8.
Primorac I, Weir JR, Chiroli E, Gross F, Hoffmann I, van Gerwen S, Ciliberto A & Musacchio A. Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. elife 2013, 2:e01030.