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Reference : UMR5247-FRELAM-001
Workplace : MONTPELLIER
Date of publication : Friday, June 19, 2020
Scientific Responsible name : Frédéric Lamaty/Séverine Chaumont-Dubel
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
The objective of the EcoSero6TSA project, at the chemistry-biology interface, is to adapt an innovative sustainable tool in synthetic chemistry, mechanochemistry, for an application in medicinal chemistry. The goal is to allow the synthesis of molecules usable for the treatment of symptoms associated with autism spectrum disorders (ASD). Mechanochemistry allows chemical reactions to be carried out in the absence of an organic solvent by using mechanical forces. This approach, innovative in medicinal chemistry, will allow the rapid preparation of a library targeting the 5-HT6 receptor of serotonin, a promising therapeutic target for the treatment of ASD, currently insufficiently supported. Once the pharmacological properties of the newly synthesized molecules and their impact on the different receptor signaling pathways characterized in vitro and in vivo by cell biology, biochemistry and immunohistochemistry approaches, the most promising will be tested for their ability to treat the main and co-morbid symptoms in two preclinical mouse models of ASD with high translational value, the mice not expressing the opioid Mu receptor (Oprm1 - / -) or expressing a mutated form of the synaptic protein Shank-3 (Shank3 ∆ex13-16 - / -).
The EcoSero6TSA project is funded by the iSITE MUSE (Montpellier University of Excellence) and is the subject of a collaboration between the Max Mousseron Institute of Biomolecules (IBMM), the Institute of Functional Genomics (IGF) and the Medical College of the Jagiellonian University in Krakow.
The research activities of the Max Mousseron Institute of Biomolecules (IBMM, https: //ibmm.umontpellier.fr) are located at the interface of chemistry and biology, focused on essential biomolecules and concern their design, their synthesis and their pharmacology. These biomolecules and their families of compounds are used as basic molecules in pharmacology for the study of the physiological and pathological mechanisms associated with them, they are also the essential precursor molecules of future drugs. At the same time, the applications of biomolecules cover vast fields such as cosmetology, food, veterinary industry and agro-chemistry which respect the environment and which are part of a framework of sustainable development (green chemistry). In this context, the Green Chemistry and Innovative Technologies team at IBMM (https://greenchem.cnrs.fr/) is dedicated to the realization and development of more environmentally friendly chemistry by calling on modern synthetic technologies such as mechanochemistry, continuous flow and microwaves. These approaches allow us the efficient and eco-responsible preparation of organic molecules, organometallic complexes and materials, using solvent-free approaches, alternative solvents and catalysis. The team notably acquired unique and pioneering expertise in organic and organometallic mechanosynthesis, at regional, national and international levels.
The Institute of Functional Genomics (IGF) of Montpellier (https://www.igf.cnrs.fr) is a fundamental research center whose research work focuses on cellular communication processes and cellular signaling, more particularly in the fields of neurobiology, cardiology, endocrinology and oncology. IGF is recognized worldwide for its past achievements in the field of G protein coupled receptors (GPCRs), in particular the glutamate and serotonin receptors.
The IGF is an institute offering all the technologies and infrastructure necessary for biochemistry, cell biology, and pharmacology experiments, as well as for physiological and behavioral studies. The IGF hosts and manages technological platforms open to the Montpellier scientific community, including a platform dedicated to virus production, a genomics platform, a small animal imaging platform, a proteomics platform and a pharmacological screening platform. and interactomics (Arpege platform). These platforms organize training sessions dedicated to users every year, thus offering a unique opportunity for training and knowledge transfer to students and researchers recruited at the start of their careers.
The thesis carried out in two internationally renowned institutes, the IBMM for the chemistry part (Frédéric Lamaty, Xavier Bantreil) and the IGF for biology (Séverine Chaumont-Dubel, Philippe Marin), will allow the candidate to '' acquire a solid multidisciplinary training, at the chemistry-biology interface and combining molecular and behavioral studies, which will be an important asset for his future career.
Constraints and risks
The thesis work will be carried out in two different laboratories in Montpellier.
In chemistry: Work in a fume hood. Mandatory wearing of a cotton blouse, protective glasses and gloves to prevent chemical risks.
In biology: work in a culture room and on animals, in laboratory anumal houses. Animal treatments may require occasional visits to the laboratory for a short period on weekends.
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