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Reference : UMR5247-MARLOP-002
Workplace : MONTPELLIER
Date of publication : Thursday, January 07, 2021
Type of Contract : FTC Scientist
Contract Period : 12 months
Expected date of employment : 1 March 2021
Proportion of work : Full time
Remuneration : 35 000 - 40 000 € bruts par an
Desired level of education : PhD
Experience required : 1 to 4 years
DNA methylation, catalysed by DNA methyltransferases (DNMTs), is an epigenetic modification involved in cancer formation and maintenance. , As nucleoside analogues, approved DNMT inhibitors (DNMTi), have limited use due to severe side-effects. Many researches to identify non-nucleoside DNMTi identified new scaffolds as DNMTi but their potency is not sufficient to envisage them as therapeutic molecules. Thinking outside the box, the main goal of this project is to synthesised multivalent DNMTi to: 1) increase DNMTi potency and access selectivity and 2) scan cellular contexts using these chemical tools via chemical-biology approaches.
- Carry out literature search for the design of synthesis pathways for multivalent DNMT inhibitor synthesis.
- Synthesise multivalent epigenetic inhibitors (functionalisation of identified DNMT inhibitors, synthesis of multivalent peptide platforms, coupling of functionalised inhibitors on the platforms).
- Characterisation of synthesised compounds (NMR, LC-MS, HPLC, IR)
- In vitro evaluation of multivalent DNA methylation inhibitors
- Design and synthesis of multivalent chemical probes targeting DNA methylation.
- Identification of therapeutic targets via chemical biology approaches (e.g. affinity protein purification)
The candidate must have a PhD at the interface of chemistry and biology. He/she must have demonstrated knowledge and skills in organic synthesis and some experience or at least a strong interest in biochemistry and biology. He/she must have ability to carry out cutting-edge multidisciplinary research project and be proactive for his/her project. He/she must be a team player with excellent communication skills and must be fluent in French or English.
This research project at the interface of chemistry and biology will be held at the IBMM institute on the research area “new epigenetic strategies for a better targeting and understanding of epigenetic modification in pathological contexts” supervised by Dr. Marie Lopez. Our research focuses on innovative strategies to target and decipher epigenetic mechanisms in pathological contexts, through multidisciplinary projects involving chemistry, biochemistry, biology and chemical-biology. We recently reported non-nucleoside DNMT inhibitors active on the purified enzymes and in cancer cell lines.
Constraints and risks
Rules of good laboratory practice.
Health and safety rules.
To apply, send a CV, a cover letter and 2 to 3 references (email and phone number) via the CNRS platform.
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