Institut Necker Enfants Malades, Centre de Médecine Moléculaire, Département « Biologie Cellulaire (croissance et signalisation) », Paris, France.
The mammalian Target Of Rapamycin (mTOR) is a master regulator of growth. During the past ten years we have generated and characterized a wide panel of mouse mutants in the mTOR pathway. We were involved in revealing specific and interesting phenotypes that increased our knowledge of mTOR roles in pathophysiology: mutants with small cells, mutants resistant to tumorigenesis in specific tissues and after specific oncogenic insults, mutants mimicking caloric restriction and promoting longevity, mutants with altered insulin action.
The overall goal of our research proposal for the next five years is twofold. From one hand we want to better understand fundamental processes including cell size control and organismal longevity. To this end we want to determine the molecular targets of the mTOR/S6 kinase cassette that may explain the alterations in cell size and lifespan when these kinases are deregulated. From the other hand we want to understand and cure rare human genetic diseases that arise from pathological changes in the activity of the mTOR pathway or that may benefit from therapeutical intervention on this pathway. These diseases include Tuberous Sclerosis Complex, metabolic diseases, lysosomal storage diseases.
Host: Prof. Lluis Fajas