Professor Dr Andrea Musacchio

Research Priorities: Cell division, chromosomes, mitotic spindle, centromeres, kinetochores
Andrea Musacchio is an Italian structural, molecular, and cell biologist. He studies the molecular mechanisms of cell division, with important implications for the study of genetic alterations in tumors and other diseases.
Andrea Musacchio’s focus in on the processes that enable errorless distribution of the genome from a mother to its daughter cells. During mitosis, chromosomes consist of two identical, connected copies. During cell division (mitosis) the chromosomes attach themselves to a framework called the mitotic spindle. The attachment involves complex structures called kinetochores. As soon as the chromosomes are all arrayed on the spindle through such attachments, they are disconnected and redistributed towards both ends on the dividing mother cell. Thus, each daughter cell inherits the same chromosomal make-up.
Musacchio’s group focuses on the study of kinetochores. Kinetochores provide the chromosomes with points of attachment onto the mitotic spindle during cell division. In addition to that, kinetochores also govern control mechanisms that correct errors during attachment to the microtubules of the mitotic spindle and that coordinate the timing of chromosome disconnection with the achievement of alignment. These mechanisms are vital for cell viability, as their suppression would lead to mistakes during the division of chromosomes, in turn causing the daughter cells to inherit the wrong number of chromosomes. Thus, kinetochores are pivotal for the inheritance of the genome and the propagation of life.
In his research, Andrea Musacchio combines biochemical reconstructions with structural and cell biological analyses to gain insight into the function of kinetochores. His working group was able to reconstitute in vitro kinetochore particles that contain all known core subunits. Similarly, it reassembled one of the aforementioned error correction mechanisms with purified components. Using X-ray crystallography and single-particle cryo-electron microscopy, Musacchio’s group determined the structures of the kinetochore’s crucial modules and used this information to introduce precise, targeted perturbations to address function. These approaches are allowing Musacchio to elucidate fundamental unknown functional aspects of kinetochore’s biology.