Élucidation des mécanismes moléculaires impliquant la signalisation en aval de mTORC1 dans le cancer.

Chercheurs boursiers - Junior 1 | Concours 2012-2013

Ivan Topisirovic

Institut Lady Davis de recherches médicales de l'Hôpital général juif


Domaine : Cancer

The activity of the mammalian target of rapamycin complex 1 (mTORC1) is frequently dysregulated in human diseases characterized by abnormal metabolism and proliferation such as diabetes, cancer and heart disease. Accordingly, compounds modulating the activity of mTORC1 hold great promise for treatments of these diseases. In recent years several of the factors, which mediate the activity of mTORC1 on cellular processes have been uncovered. Notwithstanding these recent advances in the understanding of the mTORC1 pathway, many of the cellular effects of mTORC1 cannot be accounted for by the actions of its known substrates. Thus, to better apprehend the intricate molecular mechanisms underlying the actions of mTORC1, in this proposal we will set out to uncover unknown substrates of mTORC1. To achieve this we will deploy a strategy in which the standard biochemistry and molecular biology techniques will be combined with mass spectrometry. We will further assess how these factors mediate the effects of mTORC1 signaling in normal versus cancer cells using the standard cell and molecular biology and biochemistry techniques. These findings should improve our knowledge of how are mTORC1 signals relayed to cellular processes, which in long-term should open new therapeutic avenues to curb dysregulated mTORC1 signaling in cancer and other human diseases.