Mario Pende, Research Director at Inserm and head of a team at the Institut Necker-Enfants malades (Paris), deciphers the molecular and cellular mechanisms induced by nutrients. This enormous task led him to rare diseases. This research has earned him two grants from the European Research Council (ERC Starting Grant in 2007 and Consolidator Grant in 2013).
Mario Pende began working on the challenge of understanding how nutrients regulate cellular mechanisms: a long process initiated nearly twenty years ago, while he was preparing his Ph.D. and then his postdoc in Switzerland. "It was at this time that I started to work in this field. I researched and cloned genes activated by dietary intake, in vitro in mammalian cells and in vivo in mice," he explains. These genes - the three main ones being mTOR, AKT and S6 kinase - code for enzymes from the family of kinase proteins. Their function and roles had yet to be discovered. So, to learn more, Pende assembled his first proposal for ERC funding in 2007, the year the program launched. As a young researcher, he was awarded a Starting Grant.
"The idea was not to distinguish between the effects of different types of nutrients on the expression of these genes, but to decrypt signaling pathways that are activated to regulate cellular functions: growth, proliferation, senescence and metabolism," he explains. Not only did the researcher describe several of these pathways, but he showed a link between these kinases and cellular aging, certain cancers, obesity, and even insulin resistance that predisposes one to diabetes.
Better understanding of rare diseases
"These proteins have a major role in human biology," he says. In addition, they are so important that their deregulation even leads to rare genetic diseases in children. This realization prompted Pende to apply for a second ERC grant in 2013. "This second project aimed to understand which of the regulation anomalies of these proteins result in these diseases, and to identify the mechanisms involved." Therefore, the researcher developed animal models and worked in close collaboration with the Hôpital Necker-Enfants malades. For example, he studied the Tuberous Sclerosis Complex, a neurocutaneous disorder that affects approximately one child in 10,000. It is due to a mutation affecting genes (TSC1 or TSC2) that control the expression of mTOR and S6 kinase proteins. It results in an abnormal proliferation of cells in different tissues and organs, such as the brain, heart and even the lungs, as well as functional disorders like epilepsy, autism and respiratory failure. He is also studying hereditary rhabdomyolysis caused by deficiency in LPIN1, an mTOR substrate, which, for an unknown reason, leads to the destruction of muscle fibers.
"To successfully carry out this work, ERC funding is extremely important. It helps researchers to complete ambitious projects because they can keep their focus on the work, without having to continuously chase after new grants. Additionally, being a grant winner offers great exposure for the laboratory, in France and internationally. Due to this ERC backing, we have regular requests for visits from foreign researchers, and this greatly enriches our network. To obtain this funding is a lot of stress, but it is a great opportunity!" concludes the happy double winner.
Learn more about Mario Pende and his work
Mario Pende leads the team for cell growth control by nutrients within Inserm Unit 1151/CNRS/Université Paris Descartes, at the Institut Necker-Enfants malades (Paris).