Post-doctoral researcher Bioinspired organic chemistry and asymmetric catalysis (M / F)

- Multi-step organic synthesis, peptidomimetic chemistry, Solid-phase synthesis, synthesis of molecular probes
- Structural and biophysical analyses
- Protein production and crystallogenesis
- Written reports
- Presentations in group seminars

Applications are invited for a research project interfacing chemistry and biology in the group of Gilles Guichard (Institutes CBMN & IECB, Univ. Bordeaux, CNRS) and in collaboration with Francoise Ochsenbein at the Institute of Integrative Biology of the Cell (I2BC, Univ Paris-Saclay). The goal is to develop and optimize functional modulators of the interactions between histones and one of their chaperones (i.e. ASF1) using a structure-guided approach (see Science Adv, 2021, 7, eabd9153), study the outcome of target engagement by these molecules and explore their therapeutic potential in cancer models. The ASF1 histone chaperone plays a crucial role in maintaining the epigenetic information carried by H3-H4 histones. The overexpression of ASF1B induces the proliferation of tumor cells and constitutes a powerful marker of poor prognosis for breast cancer. These properties make ASF1 a potential target of therapeutic interest which motivated the design of a first generation of peptide-based inhibitors. However, these peptides are degraded rapidly in vivo by proteases and have limited capacity to penetrate cells, requiring optimization of their pharmacological properties. These optimized inhibitors will also serve as a basis for the development of new molecular probes (clickable, fluorescent) to explore the role of ASF1 in cells.

This project, which combines peptidomimetic chemistry and chemical biology will be conducted in the Guichard group (https://www.guichard-iecb.fr/ ), a group leader at both CBMN and European Institute of Chemistry and Biology (IECB). CBMN and IECB are highly dynamic and interdisciplinary research centers located on the campus of the University of Bordeaux, France. The Guichard laboratory is well equipped for organic synthesis with access to all technological platforms of the Institute, which combine cutting-edge instrumentation in physicochemical analysis (NMR, mass spectrometry, X-ray diffraction, etc.).

This is a project funded by the National Research Agency (ANR) and the Région Nouvelle Aquitaine. The project associates in a very complementary way the group of Françoise Ochsenbein at I2BC. We anticipate that part of the work (biophysical measurements and structural biology) will be conducted in Françoise Ochsenbein's laboratory as part of secondments at I2BC.