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The objective of the study is to evaluate HCMV infection in different cell models from cell lines or derived from stem cells and to compare the results with ex vivo placental models to select the best cell system intended to be: i) reproducible, ii) easily available, iii) easy to use on a routine basis and iv) allowing prediction of transmission inhibition from mother to fetus.
Based on these results, an antibody functionality assay based on a neutralization assay or on a cell to cell spread inhibition assay using the selected cell models will be developed, optimized and implemented to test different serum samples from sero-epidemiological studies or preclinical vaccination studies to decipher the role of antibodies in virus maternofetal transmission/non-transmission and to identify biomarker candidates of congenital infection prevention.
The candidate will be provided with an open, free-thinking, rigorous and supportive environment both in academic and industrial research settings that will aim at fostering scientific excellence. He/she will have an excellent opportunity to develop his/her skills in state-of-the art cell culture technology and to publish high-impact results that might ultimately translate into novel assay for the clinical monitoring of vaccine candidates.
Key accountabilities:
Development of the cell model
-Select the most pertinent models to develop based on a bibliographic review.
-Develop the cellular models and characterize in terms of morphology, viability and expression of critical trophoblast markers (immuno-fluorescence, gene expression).
-The cell model can be derived from cell lines or stem cells, in 2D or 3D system, composed of differentiated cells or not, a mixture of different cell origins (cytotrophoblast, syncytio-trophoblast, vascular endothelium). The model should also include investigations on the endothelial cells, i.e. the first targeted cell type on the maternal side, as well as fetal neural cells, i.e. the last targeted cell type at the fetal side.
-Optimize culture conditions and freeze/thaw protocols.
-The final cell model should be easily available, easy to handle in 96-well format and reproducible.
Infection by HCMV
-Define a protocol for cell infection, characterize the cell infectivity (yield, type and % of infected cells, kinetics) and compare the results with ex vivo placental models.
-The final model should mimic infection in ex vivo placental models.
Development and validation of the antibody functionality assay
-Develop, optimize and implement an antibody functionality assay based on a neutralization assay or on a cell to cell spread inhibition assay.
-Serum samples obtained from sero-epidemiological studies or preclinical vaccination studies as well as mAb panels will be tested in these assays to decipher the role of antibodies in transmission/non-transmission of the virus to the fetus and to identify biomarker candidates of congenital infection prevention.
-As an alternative, if the identified specific cells are not easily available or easy to use on a routine basis, the scope of this work will be to demonstrate that the available high throughput neutralizing assay using epithelial cell line (ARPE-19) is representative enough and lead to the same conclusions on vaccine-induced antibody functions.
Expected Qualification / Experience:
The candidate will have a PhD (or be in the process of completing it) in a relevant area such as cell biology expert in placenta cells area, congenital infection or any other related field with an outstanding academic track record/evidence of potential. He will have excellent organizational and interpersonal skills, with ability to analyze or research complex issues, interpret scientific data and write factual reports. He should also have experience in primary cell culture and viral infections.
It will be a fixed-term position for 2 years with part of the work conducted at Sanofi Pasteur (Marcy l’Etoile - France) and part at CHU Dupuytren (Limoges - France).
The candidate will be required to upload a CV and supporting statement as part of his/her online application.
Skills:
Expertise in placenta cell biology preferably from human sources
Experience with virus infection or at least comprehensive background in virology
Good communication skills, contribution to the preparation and presentation of scientific updates to senior management and /or the scientific community
Capacity to integrate labs with different culture and environment
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24-03-2024
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