Viral replication and transcription are key steps of the viral cycle. Hélène Malet analyses the structure of viral proteins involved in these processes, in particular viral polymerases. During her thesis, carried out under the supervision of Dr. Bruno Canard at the AFMB, Marseille, she characterized by X-ray crystallography a polymerase structure of the Flaviviridae family, to which the Dengue virus belongs. Then, eager to learn a complementary method of structural biology, she did a post-doctorate in electron microscopy in the laboratory of Pr. Helen Saibil at Birkbeck College, London. Since then, she combines her interest in electron microscopy and viral replication. She undertook a post-doctoral fellowship on the structural analysis of Peribunyaviridae polymerase in the group of Dr. Stephen Cusack at EMBL Grenoble, before being recruited as an UGA Associate Professor at IBS in the team of Dr. Guy Schoehn in the Electron Microscopy and Methods group.
Her research project focuses on the structural and functional analysis of bunyavirus replication, a viral order consisting of many highly pathogenic human viruses against which no drugs or vaccines are available. The latest advances in electron microscopy and the presence of state-of-the-art electron microscopes at IBS and ESRF enable to determine high-resolution structures of these essential enzymes thereby revealing their modes of action, a key step for the future development of anti-virals. In the longer term, this project aims to understand the mechanisms of interactions between viral proteins and host proteins involved in the regulation of viral replication, combining high-resolution electron microscopy of isolated particles and cellular electron microscopy, allowing an integrative view of these processes. This project is financially supported by the ANR (HiPathBunya) and will make an extensive use of IBS technology platforms managed by ISBG and funded by FRISBI and Gral. The appointment at the IUF will allow her to devote more time to this project.