CV Science

Evelyne MANET PhD Molecular and Cellular Biology

Course and current status

Titles and qualifications

2002 : Habilitation à Diriger des Recherches, Claude Bernard University, Lyon I.

1983 : PhD in Molecular and Cellular Biology, Claude Bernard University, Lyon I.

Carreer

Since 2013: Research Director (DR2) at CNRS,, Group leader of the team "Oncogenic herpesviruses", International Center for Research in Infectiology (CIRI), INSERM U1111, CNRS UMR5308, University of Lyon, ENS-Lyon.

2006-2012:  Research Director (DR2) at CNRS, group leader of the team "Molecular Biology of gamma-Herpesviruses", Human virology unit, INSERM U758, ENS-Lyon

1994-2005 : Chargée de Recherche CNRS, Human virology unit, INSERM U412, ENS-Lyon, in the "human gamma-herpesviruses" team directed by Dr A. Sergeant.

1988-1993 : Chargée de Recherche CNRS, Molecular and Cellular Biology Unit, UMR49 CNRS/ENS, ENS-Lyon, in the "human gamma-herpesviruses" team directed by Dr A. Sergeant.

1985-1987 : Post doctoral fellow in the Molecular Virology unit, UM30 CNRS, directed by Pr J. Daillie,Lyon. 

1983-1984 : Post doctoral fellow à l’EMBL, Dr V. Pirrotta 's team, Heidelberg, Germany.

Scientific summary

Main research theme: Molecular Biology of Epstein-Barr virus (EBV)

Epstein-Barr virus (EBV) was the first virus shown to be associated with a human tumour, the Burtkitt’s lymphoma (BL) in 1964. Since, this ubiquitous human γ-herpesvirus (90-95 % of the adult human population is infected) has been shown, to be associated with other human malignancies both in immuno-competent individuals (undifferentiated nasopharyngeal carcinoma (NPC), Hodgkin's disease (HD), rare T-cell and NK-cell lymphomas, gastric carcinomas) and in immuno-compromised individuals (lymphoproliferations and lymphomas) in particular post-transplant patients (PTLD: Post-Transplant Lymphoproliferation Disease). The primo-infection is usually asymptomatic when it occurs in childhood but later in life can result in Infectious Mononucleosis (MNI). After primo-infection, the virus persists in a life-long latent state (in memory B cells) in infected individuals with intermittent viral production occurring in the oropharynx.

Interestingly, EBV has the unique capacity to induce indefinite proliferation (immortalization) of quiescent human B-lymphocytes, upon their in vitro infection, leading to the establishment of lymphoblastoid cell lines (LCLs) whose phenotype is very similar from that found in PTLDs.

I have now been involved in EBV research for more than 20 years working both on the mechanisms of immortalization of quiescent human B cells by the virus and on the characterization of important steps of the productive cycle of EBV.

Major achievements in the field:

1) The identification of the viral proteins, EB1 (BZLF1 gene) and R (BRLF1 gene), as key activators of the EBV lytic cycle; 2) the identification of RBP-Jkappa as a cellular protein targeting EBV EBNA2 to its responsive sites on the DNA; 3) the characterization of EBNA3 proteins as transcriptional repressors and the demonstration of their antagonist effect on EBNA2’s transcriptional activation; 4) the identification of the early EBV protein EB2 (BMLF1 gene) as a viral mRNA export factor essential for virus production; 5) the characterization of the cellular protein RBM15b/OTT3 as a new mRNA processing factor; 6) the characterization of a previously unknown cellular protein, ubinuclein, as a member of the NACoS (Nuclear and Adhesion junction Complex components) and as  a modulator of EBV’s reactivation in epithelial cells; 7) The characterization of a TBP (TATA binding protein)-like viral protein required for expression of late EBV genes; 8) More recently by using a high throughput yeast two-hybrid screen my team has identified novel relevant cellular partners for the EBNA3 and EBNA1 proteins that are still under investigation.

Skills: molecular and cellular biology relevant to the study of transcription factors, proteins involved in mRNA processing. Protein/protein interactions. Construction and manipulation of EBV- recombinants.