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TU Dresden » Faculty of Mechanical Science and Engineering » Institute for Materials Science » Chair of Materials Science and Nanotechnology

Friday, 20 January 2017
(at 11:00 in room Auditorium, Pfotenhauerstr. 108 (MPI CBG))
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Why fat does not accumulate in the muscle of a healthy vertebrate? A systems biology approach

Prof. Gianni Cesareni

University of Rome Tor Vergata

Muscle regeneration is governed by a complex crosstalk among dozen and more cell types. Fibro-adipogenic precursors (FAPS) play an important role in this process by positively regulating the activation and maturation of satellite cells, the muscle progenitor cells. FAPs, however, when cultured i/n vitro/, show a remarkable capacity to differentiate into adipocytes and fibroblasts. FAPs, indeed, are held responsible for the deposition of fat and fibrotic infiltrates in the degenerating muscles of dystrophic or old individuals. Fat depositions, however, are not observed in the interstitial regions between the fibers of healthy muscles of young individuals.
We have modeled by a system of differential equation the process of muscle regeneration. The model takes into account the complex network of interactions between the different mononuclear cells that are resident in the muscle or are attracted to the muscle following damage or chronic strain. This model faithfully represents the activation kinetic of the different muscle cell types but predicts the accumulation of adipocytes, which is not observed in physiological conditions. By purifying the different muscle cell types and by testing them in pairwise combinations we have shown that myotubes negatively control FAP differentiation by activating the NOTCH pathway. Remarkably adipogenesis of FAPs from a murine dystrophy model cannot be controlled by the NOTCH ligand, providing a rational basis for the observation that dystrophic patients, with age, accumulate fat and scars in the muscle tissue. I will provide evidence of the molecular basis in this defect in differentiation control.

Announcement (pdf)

Brief Bio:

Gianni Cesareni is a Full Professor of Genetics at the University of Rome Tor Vergata (Italy). After obtaining a degree in physics at the University of Rome La Sapienza he spent three years in Cambridge in the laboratory of Sidney Brenner. He then moved to the EMBL in Heidelberg where for nine years he led a group working on the mechanisms controlling plasmid DNA replication. Since 1989 he teaches and works in Rome. He has been interested in the interplay between specificity and promiscuity in the protein interaction network mediated by protein recognition modules. Over the past couple of years a large fraction of the group has focused on a project aimed at understanding the process of muscle regeneration from a systems perspective. He is a member of the European Molecular Biology Organization. He is a recipient of an ERC advanced grant.

Invited by G. Cuniberti

Within the nanoSeminar

last modified: 2021.10.02 Sat
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