Description du sujet de thèse

Titre. Design and synthesis of multivalent epigenetic inhibitors

Contexte. Epigenetic enzymes were identified as therapeutic targets in various diseases, including neurodegenerative diseases, schizophrenia, cancer and more recently in pulmonary and inflammation diseases. But selective targeting of epigenetic enzymes, e.g. HDACs, DNMT, and the understanding of the relative implication remain controversial and unaddressed. In this context, the aim of this PhD project is to design and synthesis multivalent inhibitors to target specific epigenetic enzyme, based on crystal structure and known inhibitors, and decipher their roles in pathological contexts. First, single inhibitors will be functionalised to be grafted on various platform. Then, inhibition activity of the multivalent inhibitors will be measured and compare to single inhibitor. Finally, impact of the such inhibitors will be evaluated in cells.

Missions. For this project, the candidate will:
- design target compounds based on literature
- synthesise functionalised epigenetic inhibitors
- synthesise libraries of multivalent epigenetic inhibitors
- characterise synthesised compounds (e.g. NMR, MS, HPLC)
- participate to the biological evaluation of the compounds in collaboration with our partner on this project

Profile. The candidate must hold a master in organic chemistry and must demonstrate interest in the synthesis of bioactive compounds. Biochemical/biological experience in the biological evaluation of active compounds would be appreciated, but is not mandatory. Candidates must have the ability to carry out research projects and be able to bring new ideas. He/she must be able to work in a team and have good communication skills. Fluency in English is required, French would be beneficial but is not essential. To apply, submit your CV including 2-3 references (email and phone number) and a cover letter.

Contexte de travail

At the IBMM, our research group focuses on chemical biology and chemistry to decipher and target epigenetic mechanisms in pathological contexts. This PhD project, funded by the ANR is part of a collaborative project involving chemists and biologists and the selected candidate will have the opportunity to participate to project meetings with the different partners and to take part of the biological evaluation of the compounds in our partners laboratories.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.