STANDBYME
Acute respiratory tract infections (ARTI) are a major global public health problem and remain the deadliest communicable disease worldwide and the first overall leading cause of death in children. The main etiologic agents of these ARTI are respiratory viruses, which cause annual epidemics but also the recurrent emergence of new zoonotic outbreaks sometimes reaching pandemic proportions. Respiratory viruses primarily enter and are transmitted through the upper respiratory tract (URT). Since respiratory viruses are intracellular pathogens dependent on their ability to efficiently hijack host cellular pathways for their replication, early host responses locally induced in the nasopharynx are major determinants of the pathophysiology and fate of viral infection.
The STANDBYME proposal leverages novel virus-based reporter tools combined with highly physiologically relevant 3D models of the URT, comparative multi-omics analyses, and siRNA knockdown in an original strategy to elucidate and characterize the key mechanisms driving the susceptibility, pathophysiology, and antiviral response of human respiratory airways to viral infections, with a particular focus on the crosstalk between infected and bystander cells. Once completed, the project will improve our qualitative understanding of the preferential modulation of specific biological processes of the host cell by respiratory viruses, either by identifying new elements in already described pathways and/or unveiling previously unknown biological mechanisms and dynamics of the infection/disease process.