Reference : UPR2301-STEDEV-003
Workplace : GIF SUR YVETTE
Date of publication : Tuesday, August 2, 2022
Type of Contract : FTC Scientist
Contract Period : 12 months
Expected date of employment : 1 January 2023
Proportion of work : Full time
Remuneration : 2743-3896 € gross salary (depending on the experience)
Desired level of education : PhD
Experience required : 1 to 4 years
As part of a Labex NanoSaclay/Charm3at project (SmartTher: Radio-activatable anti-cancer therapy), a 12-month postdoctoral research position in organic chemistry is available. This project, which ranges from the chemical synthesis of compounds to preliminary in vitro evaluations, focuses on designing anti-cancer drugs that can be activated by ionizing radiation and that target tumors for applications in radiotherapy/chemotherapy.
The candidate will integrate, at the ICSN, a group from the Department of Chemobiology composed of 3 permanent researchers. The effectiveness of these molecules in medical physics will be evaluated by a team from ISMO that studies anti-cancer compounds in cellulo under irradiation.
Context of the research project:
One out of two cancer patients is treated with radiotherapy. This treatment is, unfortunately, the cause of side effects on the surrounding healthy tissues and is not very effective on radioresistant cancers. Recent developments bring new avenues for greater efficiency, such as combining ionizing radiation with nano-objects based on heavy atoms (Z>50), amplifying the effects of ionizing radiation, or using pro-drugs of radiation-activatable cytotoxic agents.
We propose, in this project, to combine these last two strategies hoping to have a synergistic effect but also to improve the targeting of chemo and radiotoxic impact on the tumor. In this perspective, we propose to develop and test multimodal, radio-amplifying macromolecules capable of targeting tumors and releasing anti-cancer agents at these tumors' levels under ionizing irradiation. These radio and chemotherapeutic compounds will make it possible to amplify the damage caused to cancerous cells while limiting the side effects to other surrounding healthy cells. Breaking with conventional protocols, they should provide a breakthrough in treating cancers that are difficult to cure, such as cancers surrounded by susceptible healthy tissue or cancers resistant to traditional treatments.
At the interface of Chemistry, Physics, and Medicine, this project is interdisciplinary and requires varied expertise to carry out the synthesis/characterization of chemical compounds, the study of their toxicity, and their biological evaluation to study the synergistic effect associating pro-drug and radio-amplifiers.
The successful candidate will be in charge of the synthesis and characterization of:
- compounds sensitive to ionizing rays (NMR/LC-MS characterizations)
- multi-anchoring peptide ligands prepared on solid supports (SPPS) (LC-MS/Maldi characterizations)
- final multimodal macromolecules (LC-MS/Maldi characterizations)
After preparation/characterization and optimization of the final compounds, the candidate will evaluate them on tumor cell lines (toxicity (MTT assays), internalization/localization in tumor cells vs. healthy cells (ICP-MS and optical imaging)). The radio-amplifying effect and the synergistic effect (radio-amplification and action of the pro-drug) will be evaluated by quantification of clonogenic survival and compared with those obtained with conventional treatments combined or not. The diffusion of macromolecules within tumors and the synergistic effect of combined treatment will also be studied (3D cell models).
She/he will be responsible for writing laboratory notebooks/reports/publications.
The candidate will need solid experience in organic chemistry but will also have to adapt to the project's multidisciplinary nature.
The candidate will have a Ph.D. in organic chemistry and research skills resulting in at least one publication as first/second author.
We are looking for a candidate with solid knowledge of organic synthesis, a good understanding of peptide synthesis, and willing to work at the chemistry/biology/medicine interface for biomedical applications.
An interdisciplinary chemistry/biology profile, particularly with peptide/pro-drug chemistry skills, will be appreciated.
The candidate must have organizational skills and a positive attitude to work in a team on multidisciplinary projects while respecting rules and procedures.
She/he should be fluent in French and English.
The Institute of Chemistry of Natural Substances (ICSN) is a CNRS Research Unit whose research axes are chemistry and biology. It is part of the University of Paris-Saclay which, since 2015, has brought together research and education establishments in southern Paris. The ICSN is located on the Gif-sur-Yvette campus and has approximately 125 agents, including 76 permanent staff, spread over three buildings. Within the Department of Chemobiology (http://www.icsn.cnrs-gif.fr/spip.php?article1280), the recruited agent will join a group of 3 researchers and three doctoral students. He/she will be placed under the hierarchical authority of the team leader. The institute benefits from a privileged working environment for activities at the chemistry/biology interface with numerous platforms and equipment (https://icsn.cnrs.fr/plateformes).
ISMO (http://www.ismo.universite-paris-saclay.fr/spip.php?rubrique1) is a joint research unit of the CNRS and the University of Paris-Saclay, bringing together 159 people, 82 of whom are permanent. The institute is a center of excellence in three major scientific fields: molecular physics and its applications, nanosciences, and physics for biology. The Nanomedicine and Biophotonics team involved in this project carries out a cutting-edge interdisciplinary activity at the chemistry-physics-biology interface. It benefits from a large fleet of equipment (lasers, spectrometers, particle beams, super-resolution microscopes, beamline in partnership with SOLEIL, etc.) and collaborations for access to different types of radiation (proton, carbon …).
Constraints and risks
The project activities will be shared between two laboratories with periods of organic synthesis at ICSN and biological evaluation of compounds at ISMO, which will involve geographical mobility between these two laboratories of the University of Paris Saclay. The two institutes are located about 2km from each other.
Two reference letters and contact details should be provided. The start date is ideally early January 2023.
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