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Propositions des laboratoires

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.idmit­cen­ 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@a­ Applications will be accep­ted until a sui­ta­ble can­di­date is found.