RESEARCH
Doctors and ResearchersRESEARCHERS
THE STORY OF PAOLO BONALDO AND PAOLO BERNARDI
The story of Paolo Bonaldo and Paolo Bernardi is an example of how Telethon selects and funds the best projects and the best scientists. At the same time, the story of the two scientists tells how winning ideas can stem from a chance encounter. Bernardi is, in fact, one of the best known Italian scientists working on the study of mitochondria. Bonaldo, on the other hand, specialises in the study of muscles. Both work at the University of Padua. Together, their research has reached the final stages and they are preparing for human trials of a cure for Collagen VI disorders.
RESEARCHERS
MARCO SANDRI – ISTITUTO DULBECCO TELETHON
DOCUMENTS
PAOLO BERNARDI ALLA MARATONA TELETHON 2017
THE ASSOCIATION
Il laboratorio del Prof. Paolo Bonaldo
Most of the cells in our body are surrounded by the extracellular matrix, a complex set of proteins that can vary from tissue to tissue and whose alterations cause a plethora of diseases. The main interest of the Bonaldo team is Collagen VI (COL6), an extracellular matrix protein which plays a key role in skeletal muscle, providing mechanical support and regulatory signals to muscle fibers. When COL6 is absent or abnormally deposited due to a mutation in one of its genes, a progressive congenital pathology characterized by muscle weakness and wasting occurs in patients as well as in animal models. The molecular characterization of the structure and functions of COL6, which are the major fields of study of the team of Prof. Paolo Bonaldo, allow the scientific community to understand which are the best therapeutic in order to find an effective cure for patients affected by COL6-related disorders. Another interest of the team is a family of proteins called “Emilins”, which have crucial role in the extracellular matrix surrounding blood vessels. Until now, there are no known human diseases due to alterations of these proteins, but it is very likely that they will be identified soon.
2016. Some of our colleagues have gone to work in other laboratories around the world, and we wish them all the best of luck! At the same time, they take their first steps with us in the world of scientific research: the recent graduates Ilaria and Francesco (junior); master’s degree trainees Manuela and Giorgia; and the very young three-year degree trainee Samuele.
2014. In this photo (from left, clockwise): Peiwen, Prof. Volpin, Francesco, Prof. Braghetta, Prof. Bonaldo, Silvia, our collaborator Andrea, Dario, Matteo, Diana, Marianna, Matilde, Sibilla, Francesca , Valeria and Martina.
Science is a teamwork: Prof. Bonaldo’s laboratory works in close contact with many national and international groups, experts muscle physiology, matrix biology or other aspects that cannot be tackled without a strong experience. Among these, the group of Prof. Marco Sandri, an expert in muscle; Profs. Raimund Wagener and Mats Paulsson, who work in Germany and with whom it is extremely pleasant to discuss topics concerning the extracellular matrix; Prof. Paolo Bernardi, an expert of mitochondria, the powerhouse of every cell; and other international teams with expertise in matrix biology and pathology, such as Prof. Florence Ruggiero (France).
Prof. Paolo Bonaldo
Prof. Bonaldo has been dedicating most of his scientific life to the study of COL6, dissecting every
Prof. Paola Braghetta
Professor Paola Braghetta is an expert in the generation of animal disease models. She is actively involved in the production of transgenic mice bearing mutations in genes coding for extracellular matrix proteins, including COL6 and Emilins. These experimental models are a peerless tool not only to understand the functions of such proteins, but also to study human diseases linked to mutations of their genes. Such models will help us in identifying novel therapeutic strategies to counteract COL6-related disorders
Dr. Dario Bizzotto, Tecnico Research Assistant
The laboratory has no secrets for Dario: his huge scientific experience is a treasure that he shares every single day with all the people of the team. He is an expert on mice and therefore provides invaluable support in the production and generation of animal models for COL6 and other extracellular matrix proteins.
Dr. Nicola Facchinello, Senior Postdoc
Nicola uses the zebrafish to study genetics and developmental biology and as a model of human diseases. The zebrafish is a successful and versatile animal model system for the generation of genetic models of human diseases. Thanks to the recent discovery of the CRISPR / Cas9 technology, an important revolution for biomedical research, Nicola is able to insert desired changes in the genome in an effective, rapid and economical way for the generation of new animal models to study COL6 and the family of proteins known as Emilins.
Dr. Matilde Cescon, Assistant Professor
Matilde is exploring the role of COL6 in non-muscular tissues, including the nervous system. Her studies allowed to understand that the impact of COL6 deficiency is not only restricted to skeletal muscles but also to peripheral nerves and to the neuromuscular junctions, the contact sites between nerves and muscles where neurotransmission occurs. Her main focus now is the design of novel therapeutic strategies targeting the neuromuscular junction in COL6-related myopathies.
Dr. Silvia Castagnaro, Senior Postdoc
Silvia is dedicating most of her work to cell cultures. She makes cells grow on different plastic supports and she supplies them with the combination of the needed nutrients, sometimes modifying their composition, in order to study how COL6 deficiency affects cell behavior at the level of cellular processes and adaptation mechanisms. The cells she studies are derived from mice lacking COL6 and from biopsies of patients with Bethlem myopathy and Ullrich congenital muscular dystrophy
Dr. Lisa Gambarotto, Postdoc
Lisa dedicates her work to autophagy, the process through which the cell digests and recycles its components. She began studying this mechanism in skeletal muscle, focusing on a key regulatory protein called AMBRA, and then focused her work on novel strategies able to reactivate autophagy in muscles of mice lacking COL6, by adding natural molecules to the diet. Recently she began to be interested in the study of autophagy also the peripheral nervous system.
Dr. Samuele Metti, PhD Student
Samuele is really passionate about extracellular matrix, and he is studying the molecular mechanisms that allow the proper production and degradation of COL6 in skeletal muscle. Indeed, it is still unknown how COL6 turnover is regulated and what are the implications of an incorrect turnover. Furthermore, Samuele is actively studying which membrane receptors are mediating the transduction of COL6 outside-in signals in muscle stem cells.
Dr. Chiara Consorti, PhD Student
Chiara’s work in the laboratory is dedicated to zebrafish, an organism with many advantages which make it ideal for research purposes. Thanks to the great number of eggs released, a rapid development and low-cost maintenance, zebrafish are suitable for large-scale drug screening. Indeed, Chiara is carrying out a large-scale repurposing study in the zebrafish model lacking COL6, based on the screening of drugs already approved and routinely used in the clinical settings to treat other human disease, in order to identify which drugs are able to ameliorate the structural and functional muscle defects.
Dr. Loris Russo, PhD Student
Among the new additions to the team we find Loris, who is interested in studying the role of COL6 in tendons, the structures which connect muscles and bones. His work focuses on the function of COL6 where muscles and tendons meet, thus forming a highly specialized interface. This site, in fact, is subjected to strong forces that challenge both muscle and tendon integrity.
Dr. Sonia Calabrò, PhD Student
Up to now the therapeutic approaches tested on animals depleted of COL6 mainly focused on the recovery of muscular defects. Sonia is investigating the efficacy of novel potential treatments aimed at ameliorating the alterations caused by COL6 deficiency in other regions, in particular at the level of the neuromuscular junction, also through the repurposing of drugs already approved for the treatment of other pathologies. The use of such drugs, whenever successful, would allow a faster translation to clinical trials.
Dr. Giulia Pigato, Postgraduate Fellow
The heart is the center of the cardiovascular system. It is the muscular organ that pumps blood throughout body, and a healthy cardiovascular system is vital for supplying the body with oxygen and nutrients. Giulia studies alterations in the heart of animals without Emilin-1, a key extracellular matrix protein expressed in heart and in blood vessels. The aim of her project is to understand Emilin-1 roles and mechanisms in the cardiovascular system.