Doctoral position A PhD position (36 months) funded by the French National Agency for Research (ANR) in the area of virology of herpesvirus (epigenetic regulation of HSV-1 latency and reactivation) to begin fall 2019 is available at the Center for Immunology of Viral Infections and Autoimmune diseases (IMVA/IDMIT) located in Fontenay-aux-Roses, France (https://www.idmitcenter.fr/fr/). Herpes simplex virus (HSV-1) is a common human pathogen, which remains a major public health problem. HSV-1 induces recurrent infections in the eyes, which results in severe ocular pathologies. Primary infection occurs in oral mucosa and is followed by a latent state of infection occurring in ganglia of the sensory nervous systems (SNS), including the trigeminal ganglia (TG). Following various triggers, HSV-1 reactivates and spreads through the SNS towards the face and the eye. When the virus reactivates in the eye, each episode of ocular herpes can affect the visual prognosis. Indeed, herpes simplex keratitis (HSK) is still today the first infectious cause of blindness in western countries. Comprehension of the molecular mechanisms that regulate the balance between latency and reactivation is crucial for the understanding of the biology of the virus. This is also a major challenge for the design of new therapeutic approaches that are designed to prevent virus reactivations rather than stopping the lytic cycle. In several recent studies, we showed that positioning and distribution of latent HSV-1 genomes in the nucleus of infected neurons are not random, with the specific association of latent genomes with promyelocytic leukemia nuclear bodies (PML NBs). PML NBs are known as nuclear sensors of multiple stresses, including viral infections. We showed that the establishment of HSV-1 latency in mice and human TG neurons correlated with the formation of PML nuclear bodies containing HSV-1 genomes (named further as viral DNA-containing PML NBs, vDCP-NBs). We have also illustrated PML NBs and the PML protein being directly involved in the chromatinization of latent HSV-1. Most of the data has been obtained in HSV-1 infected wild type mouse models or from cell culture. The aim of this project is to use to perform HSV-1 infections in PML KO mice, to understand the role of PML NBs in the control of HSV-1 biology in an in vivo model.
The applicant must have a Master 2 focused on microbiology and/or cell biology with a focus on epigenetics. Applicants should have been among the best ranked in their respective Master. Ideally, applicants should have been allowed to compete for the doctoral school BMIC for Ph.D. thesis contracts. The applicant must be comfortable with the idea of performing animal experimentation, possess excellent problem solving skills ; able to work with minimum supervision, but however must have good teamwork skills.
To apply, please submit a CV stating explicitly your scientific skills to Patrick Lomonte and Marc Labetoulle (marc.labetoulle@aphp.fr). Applications will be accepted until a suitable candidate is found.