Dr. Fredéric Relaix studied molecular biology and biochemistry at the University of Paris VI followed by a Masters degree in developmental biology. He then went to the Mont Sinaï Hospital in New York, initially as a cooperation scientist then to complete a PhD studying the phenomenon of apoptosis and inflammation in muscle tissue. It was at this time that he started pondering over the following: how does an immature cell become destined to the muscle lineage and how are transcriptional regulation networks and PAX proteins involved.

He returned to Paris in 1998 to pursue a post-doctorate in Margaret Buckingham’s laboratory at the Pasteur Institute. Here he investigated the role of PAX proteins in muscle specification, development and survival. He has held a position at the French National Institute for Health and Medical Research (INSERM) since 2000 and in 2006 became research director (DR2) and laureate of the ‘Avenir’ research programme.

 

 

When he left the Pasteur Institute in 2006, he had several propositions from France, Japan and the USA. However, he chose the Myology group (UMR-S 787), which precedes the future Myology research center and is directed by David Sassoon. This will allow him to combine his fundamental research with more applied research (physiopathologies, clinical research and biotherapies). One of the main points of this future research institute is that everyone will be gathered in the same place. The laboratories will have an open plan allowing researchers, PhD students, post-doctorates and technicians from different groups to easily integrate. The objective of this setup, which is uncommon in France, is to encourage informal discussions, promote new collaborations and share technical and expert resources. Another aim of this project: expand the center, a very interesting prospect according to Frederic who has discussed the idea with other researchers.

 

Muscle is an ideal system for Frederic to study the mechanisms of cell fate decisions : while cell culture systems have lead to the identification of key factors involved in muscle specification, and pathologies contribute largely to our understanding of what happens in normal situations, little is known about these molecular processes in vivo. The aim of Frederic's team is to identify the genes and molecular networks involved in muscle specification, renewal, differentiation and survival using the mouse as an animal model.

 

In fact, this thematic began in Margaret Buckingham’s laboratory at the Pasteur Institute where Frederic established a colony of genetically modified mice. Cells were extracted from these mice, allowing studies at the molecular level. For example, he tried to understand how satellite cells appear with time, and has identified a population of embryonic and fœtal progenitor cells that give rise to these satellite cells. When these foetal cells become satellite cells, they become localized under the basal lamina at the fiber periphery. In this position, the satellite cell stops proliferating, becomes quiescent and acquires stem-cell properties. In the event of muscle damage or repair, they become mobilized and enter the cell cycle, self renew and regenerate new fibers. Frederic and his team are trying to understand which genes are involved in these changes, and in particular, those that control satellite cell quiescence and those that are involved in cell cycle exit. They are also trying to understand how a reversible state of cell cycle exit exists. In order to answer these questions, they are using existing animal models as well as generating new lines in the laboratory.

 

They are also interested in certain forms of muscle tumours in which cell cycle exit does not occur, thereby blocking fiber formation, deregulates and produces a rhabdomyosarcoma. Frédéric is interested in alveolar sub-types which are due to translocations between PAX genes (involved in cell specification) and other transcription factors. The mutated PAX protein has a modified transcriptional activity. Target genes are deregulated, producing a tumour. By understanding which genes are deregulated in this tumour, they will gain insight into what occurs in the normal state when one stem cell becomes a differentiated cell of the muscle lineage.