PhD Position Available for Research in Supramolecular Chemical Biology at the University of Montpellier, France (Institut des Biomolécules Max Mousseron)

Context. The SMART project (“Smart nanoparticles delivering siRNA to treat gastrointestinal stromal Tumors”) is funded by the Inter-Disciplinary & In-Lab Graduate Program of Université de Montpellier with 2 mirror PhD positions starting in 2024: one in Chemistry @IBMM (UMR5247, P.I.: Sébastien ULRICH) and one in Biology @PhyMedExp (UMR9214, P.I.: Prisca BOISGUERIN).

Overview of the project. The design of smart vectors of nucleic acids that degrade in cells at the appropriate place and within the appropriate time-scale is a major current challenge to improve the performances of nucleic acid therapies. The current strategies enable only 1-2% of the nucleic acids to be released in cells, thus leaving huge opportunities for improvement.
This PhD project rests on our recent achievements in making smart pH-sensitive peptide conjugates as vectors of siRNA (ANR-funded project NanoCard, 2022-2025, manuscript in preparation). In this new project, we will tackle the engineering of multi-dynamic peptide-based conjugates with improved sensitivity and controlled degradation. The candidate will focus on implementing a rich set of dynamic covalent reactions in order to optimize the sensitivity of the vectors to various degradation processes that will improve the siRNA release. The work will involve the synthesis of modified peptides and dynamic covalent conjugates (SPPS, HPLC chromatographies, NMR, LC-MS, UV-Vis spectroscopies), the determination of their kinetic of degradation, and the in vitro evaluation of siRNA complexation and release (gel electrophoresis, DLS, potential measurement). A close collaboration with the mirror PhD in biology will contribute to this interdisciplinary project.

Host laboratory. The Institut des Biomolécules Max Mousseron (IBMM) is devoted to research in biomolecular systems for health applications. In this context, we develop dynamic covalent assemblies and conjugates for gene delivery applications (see for instance: Chem. Eur. J., 2023, 29, 7, e202202921; ChemBioChem, 2023, 24, 19, e202300333; Angew. Chem. Int. Ed., 2021, 60, 11, 5783-5787; Acc. Chem. Res., 2019, 52, 2, 510-519).

Ph.D. candidate. You have recently graduated (M.Sc., Ecole d’Ingénieur) with excellent theoretical and practical knowledge in bioorganic chemistry (synthesis, purification, characterization). You have a strong interest for the interface with biology, with a desire to learn and practice. You are a self-starter, working autonomously, willing to take initiatives and eager to work in a multidisciplinary project. You show a clear enthusiasm for research. You are a team player with very good communication skills. Knowledge of French would be useful but is not essential. Starting date: October 2024 (flexible), salary: ca. 2100 €/month.

Interested? Applications to the SMART project must contain 1) a cover letter, signed and date, 2) a CV/resume, and 3) the transcripts of L3, M1, M2 with rankings, and be sent by email to idil-team@umontpellier.fr. APPLICATION DEADLINE: 15 APRIL 2024, 2:00 pm. For more information, contact Dr. Sébastien Ulrich (sebastien.ulrich@cnrs.fr).

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