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Reference : UMR5535-FRACOU-033
Workplace : MONTPELLIER
Date of publication : Monday, January 13, 2020
Type of Contract : FTC Scientist
Contract Period : 24 months
Expected date of employment : 1 March 2020
Proportion of work : Full time
Remuneration : 3767 € brut 3038 € net
Desired level of education : PhD
Experience required : 1 to 4 years
The post-doctoral fellow's main aim will be to decipher the effects of innovative drugs targeting RNA-binding proteins drugs on:
-phenotype and functions of immune cells
-in different mouse models of inflammation (DSS, CIA, psoriasis models, etc.)
-in different organs (immune cells isolated from spleen, lymph nodes, gut, skin, etc.)
-and also in humans: in vitro experiment and assessment in patients treated with these drugs
The post-doctoral fellow's work will thus help to better understand the mechanism of action of these drugs, to define the patients most susceptible to respond to therapy and/or to predict potential side effect to monitor.
-Work on mice and on human samples.
-Flow cytometry and cell culture.
-Flow cytometry: The applicant should have a strong background in FACs. Any experience with CyTOF would be appreciated.
-Cell culture (cell differentiation i.e. macrophages, co-cultures, etc.)
-Histology: IHC, IF
-Mouse dissection to isolate immune organs (lymph nodes, Peyer's patches, etc.)
-Western-blot, CBA, ELISA
The post-doctoral fellow will join the IGMM, which is a plurithematic CNRS research unit, offering an environment perfectly suited to the development of the proposed subject. This unit located on the CNRS campus/ Route de Mende in Montpellier is part of a rich scientific environment composed by the various institutes (IRIM, CRBM, CEFE, etc). In addition, several technical platforms (flow cytometry, imaging, metabolism, etc.) are available and complete the site.
More specificallyn the post-doctoral will integrate a cooperative Lab CNRS-ABIVAX (public – private) exploring the potential of innovative drugs targeting RNA-binding proteins on inflammation and virus. This is a very exciting project as some of these drugs are already in clinical phases in humans (HIV, ulcerative colitis and rheumatoid arthritis). ABX464, its most advanced compound, was evaluated in Phase II clinical trials and is a first-in-class oral small anti-viral molecule which blocks HIV replication and controls inflammation in ulcerative colitis. While initially selected for its ability to target RNA Binding Proteins (RBPs) involved in viral RNA biogenesis, ABX464 was shown to bind Cap Binding Complex (CBC) involved in splicing and export of human mRNAs. miRNA analysis revealed that ABX464 specifically regulates mir-124 expression, with a significantly increased (about 13 folds). As miR-124 is a modulator of monocyte and macrophage activation, we tested the anti-inflammatory properties of ABX464. ABX464 treatment dampened inflammation in Dextran sulfate sodium (DSS)-induced colitis as well as in Collagen-induced arthritis (CIA), a model of rheumatoid arthritis. A Phase IIa clinical trial to determine its efficacy in patients with Rheumatoid Arthritis is ongoing. We are currently deciphering the effects of ABX464 and miR-124 on immune cells and inflammatory process. The cooperative Lab is composed of 15 peoples with broad and diverse domains of expertise ranging from RNA, chemistry, imaging to immunology. Regular meetings and talks allow everyone to learn and progress.
Constraints and risks
The proposed experiments will be carried out mostly in ZEFI laboratory and will therefore require staggered schedules.
Handling human cells requires up-to-date HBV vaccination.
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