Voici une offre de poste de technicien au sein de l'équipe IMT de l'UMR 7292 du CNRS
DEVELOPMENT OF NEW ANTIBODY-DRUG CONJUGATES
Offer type: technician
Financing: Public: Centre-Val de Loire Region
Salary range: 1203-1831 € monthly net income, according to the candidate experience
Recruiting organization: UMR7292 GICC CNRS - Université de Tours, Equipe « Innovation Moléculaire et Thérapeutique » (IMT)
Workplace: TOURS - FRANCE
Skill area: therapeutic chemistry, organic chemistry, heterocyclic chemistry
The scientific activity of our UMR, GICC (Genetics, Immunology, Chemistry and Cancer) is based on an interdisciplinary approach ensured by clinicians, biologists and chemists. This UMR includes 38 permanent staff. Our team « Innovation Moléculaire et Thérapeutique » (IMT, 7 permanent staff), directed by Pr. Marie-Claude Viaud-Massuard, is made up of therapeutic and organic chemists, and is part of two Labex (MAbImprove, and SynOrg). The IMT team is specialized in the design and synthesis of small heterocyclic antitumor regulators (e.g. kinases or STAT5 inhibitors). Our expertise in heterocyclic and medicinal chemistry ranges from the development of new organic synthetic methodologies to in silico-assisted lead discovery and optimization. Our team has also an expertise in bioconjugation of small cytotoxic molecules to therapeutic antibodies (mAbs) via a suitably constructed spacer arm (linker) to form antibody-drug conjugates (ADCs). These skills allowed us to design and synthesize new site-specific heterobifunctional linkers permitting access to homogeneous ADCs, from any native antibody (patented methodology). We also developed an analytical physico-chemical platform dedicated to ADC analysis.
Subject of the project:
A grant from the Centre-Val de Loire Region is available in our team (IMT), as part of the project “ADC-AgroMed” directed by INRA, Bios Group (Dr Pascale Crépieux). This grant is dedicated to a 1-year technician fellowship starting as soon as possible, under the supervision of Dr. Nicolas Joubert. This work will focus on the development of original antibody-drug conjugates (ADCs).
In our team, we recently generated homogeneous ADCs through an in-house patented methodology. Actually, using this methodology, from trastuzumab (anti-HER2 antibody) we generated 6 ADCs, including 3 as active as T-DM1, all of them exhibited in vitro an EC50 below 30 pM in SK-BR-3 HER2 over-expressing cell line.
Following this success in oncology, we want to design original ADC for application beyond oncology.
For this new project, we will design and synthesize new payloads (active molecule) following SAR studies. After their biological evaluation, we will graft the active molecules on antibodies through a spacer (linker), and test the biological activity of the resulting ADCs.
We already have all the active collaborations needed for this project, including the biologists for the generation of antibodies and the biological evaluations of our ADCs on the particular models of interest (in vitro and in vivo), as well as a chemical analyst (spectroscopy analyses of ADCs). The candidate will be in charge of the organic synthesis of the payload and the linker-payload entities. The applicant will also be responsible for the bioconjugation of the linker-payload entities to the mAb. ADCs characterizations and biological evaluations on in vitro and in vivo models will be carried out by different partners of this national interdisciplinary scientific program.
The candidate must have a good knowledge of organic chemistry. Knowledge in chemical biology (bioconjugation) will be really appreciated but is not mandatory, as the main challenge of this project will be the organic synthesis of the original payloads and their grafting on their linkers, and bioconjugation will be taught if necessary. The candidate must be very motivated and able to make experiments with great care and reproducibility (needed for bioconjugation). The candidate must demonstrate a high degree of motivation for working in an interdisciplinary project, and master organic synthesis including purification techniques (flash chromatography and HPLC) and analytical techniques (especially HPLC).
Nicolas JOUBERT, MCU
UMR7292 GICC CNRS - Université de Tours
Equipe « Innovation Moléculaire et Thérapeutique »
UFR des Sciences Pharmaceutiques
31 avenue Monge, 37200 Tours
Phone: 33 (0)2 47 36 72 28
Fax: 33 (0)2 47 36 72 29
Keywords: cancer, therapeutic chemistry, organic chemistry, heterocyclic chemistry, bioconjugation, chemical biology.