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Reference : UMR7199-ANTKIC-001
Workplace : ILLKIRCH GRAFFENSTADEN
Date of publication : Tuesday, June 8, 2021
Scientific Responsible name : Benoît Frisch and Stéphane Bellemin-Laponnaz
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Title: "Hydrogels for localized release of NHC-platinum complexes targeting mitochondria to combat glioblastoma"
The main objective of the Hydro-NHC project is to develop solutions that can simultaneously eradicate cancer cells and cancer stem cells (CSC) from glioblastoma, by applying localized treatment. To address this issue and on the basis of our previous results and hypotheses, we propose to develop organometallic complexes of type metallo-carbene -based on platinum- which induce mitochondria-dependent apoptosis in malignant cells. These complexes will then be formulated and integrated into biocompatible hydrogels based on albumin or hyaluronic acid, allowing prolonged local administration of the therapeutic agent in the heart of the malignant tissue, avoiding the need to cross the blood-brain barrier (BBB).
The thesis will be carried out in partnership between the 3Bio team (Faculty of Pharmacy, Illkirch) and the team "Metals and their functions" of the IPCMS (Strasbourg) and ranges from organometallic chemistry to biology studies through formulation and characterization of biomaterials.
1- Bellemin-Laponnaz, S. N-heterocyclic carbene platinum complexes: a big step forward for effective anti-tumor compounds. Eur. J. Inorg. Chem. 2020, 10-20.
2- Wantz, M.; Bouché, M.; dahm, G.; Chekkat, N.; Fournel, S.; Bellemin-Laponnaz, S. N-Heterocyclic Carbene-Polyethyleneimine (PEI) Platinum Complexes Inducing Human Cancer Cell Death: Polymer Carrier Impact. Int. J. Mol. Sci. 2018, 19, 3472.
3- Chekkat, N.; Dahm, G.; Chardon, E.; Wantz, M.; Sitz, J.; Decossas, M.; Lambert, O.; Frisch, B.; Rubbiani, R.; Gasser, G.; Guichard, G.; Fournel, S.; Bellemin-Laponnaz, S. N-Heterocyclic Carbene-Polyethyleneimine Platinum Complexes with Potent in vitro and in vivo Antitumor Efficacy. Bioconjugate Chem. 2016, 27, 1942-1948.
4- Aloui E. Frisch, B., Lavalle Ph. De Giorgi M. Schaaf P. Protein-based biomaterial with viscoelastic behavior, process for obtaining it and uses thereof. European patent application EP19306387
The candidate will be co-supervised by Dr. Heurtault and Bellemin-Laponnaz and the thesis project is based on two synergistic and complementary teams (chemistry and biology).
- The synthesis of platinum derivatives will be carried out within the UMR 7504 Research Unit (Strasbourg Institute of Materials Physics and Chemistry (IPCMS), Cronenbourg Campus) in the Organic Materials department under the supervision of Dr Stéphane Bellemin-Laponnaz (DR CNRS; http://www.ipcms.unistra.fr). His research area is focused on the development of transition metal complexes and their applications.
- Cellular studies will be carried out within UMR 7199 (Laboratory for the design and application of bioactive molecules (CAMB)) in the 3Bio team (Biovectorization, Bioconjugation, Biomaterials; https://camb.cnrs.fr/la- research / 3bio /) under the supervision of Dr Béatrice Heurtault (MCU, UNISTRA, HDR, authorized to experiment on animals). This team has a strong expertise in the delivery of active ingredients by nanoparticulate vectors (liposomes, lipid nanocapsules, micelles, ...) as well as in innovative galenic forms (hydrogels, protein implants, ...) and in biology and particularly immunology .
The 2 teams have all the equipment, expertise and supervision necessary to carry out the various stages of the project.
Constraints and risks
The doctoral student will be subject to the internal regulations of the 2 laboratories with regard to all hygiene and safety rules. Travel between the 2 teams involved (Cronenbourg-Illkirch) is to be expected.
- The candidate must be motivated to carry out a research project in a multidisciplinary context at the chemistry / biology interface. He / She must register at Doctoral School n ° 222 (Chemical Sciences, Strasbourg) and follow the modalities of this ED with regard to doctoral training. Note that the thesis is funded by the Interdisciplinary Thematic Institute (ITI) HiFunMat to which the 2 teams are attached.
We are looking for a candidate:
- With knowledge in cell biology (cell culture, viability assay, RT-qPCR,…), in immunology (ELISA, Elispot,…) and an opening towards synthetic molecular chemistry.
- Motivated by interdisciplinary experimental work,
- A curiosity for research, a critical mind, and good writing and communication skills.
- Application deadline: June 25, 2021
- Candidates must provide a CV, a master's transcript, a cover letter and the email contact of the referents who have supervised their work in the laboratory.
Contacts: Dr. Béatrice Heurtault (firstname.lastname@example.org) and Stéphane Bellemin-Laponnaz (email@example.com).
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