Alan Wacquiez

I am currently a Postdoctoral Associate in the Saeed Lab located at the National Emerging Infectious Diseases Laboratories (NEIDL) of Boston University.

Born in the city of Nantes in France, I obtained my Ph.D. degree from the University of Tours, France, in 2020. My research during this time investigated the molecular interactions between the influenza virus non-structural protein 1 (NS1) and double-stranded RNA molecules. Using gel shift assays, I demonstrated the formation of high affinity complexes between NS1 of different clinically relevant viral strains and double-stranded RNA species containing sequences of the virus and host origin. Structural resolution of these complexes by X-ray crystallography allowed me to conclude that NS1 induces a curvature in its RNA-binding partners. Overall, this work advanced our understanding of how influenza virus NS1 recognizes double-stranded RNA molecules and thereby contribute to interferon antagonism.

After my Ph.D., I joined the “Respiratory Infection and Immunity” research team in the laboratory of Dr. Mustapha Si-Tahar at the Research Center for Respiratory Diseases (CEPR) in Tours, France, for a short postdoctoral stint. There, I studied the role of succinylation, a post-translational protein modification, in influenza virus infection and its involvement in anti-viral immunity. These studies showed that influenza virus causes metabolic alterations, particularly in the Krebs cycle, inducing the accumulation of various cellular metabolites, including succinate. The accumulation of succinate disrupts the influenza virus lifecycle and reduces the infectious particle production. In-depth mechanistic studies revealed that succinate causes succinylation of the viral nucleoprotein (NP), an essential protein required for protection of the viral genomic RNA from innate immune detection. Once succinylated, NP cannot bind with its RNA partners and remains confined in the nucleus of the infected cell.

In the August of 2022, I joined the laboratory of Dr. Mohsan Saeed, where I am currently exploring the role of viral and host protease in shaping virus-host interactions. Using a highly advanced proteomics approach, the Saeed lab identified several host proteins cleaved during viral infections. I am employing an array of molecular biology and systems biology approaches to decipher the function of these host targets in antiviral defenses and virus replication. These studies are expected to yield new insights into the virus-host biology and identify targets for antiviral drug development.