Offer Description
Supervisor: Dr X. Guillory (PI); Remuneration: 580€ net/month; Duration: 6 months between January & July 2027
Scientific background – Mitochondria produce most of the cell’s ATP through oxidative phosphorylation (OXPHOS), centered on Complex V, the mitochondrial ATP synthase. Our collaborator, Dr G. Bertolin (IGDR, UMR CNRS 6290), has shown that a particular kinase localizes inside mitochondria, where it physically and functionally interacts with the ATP5F1A and ATP5F1B subunits of Complex V to sustain ATP production and cancer cell viability.[1] Current inhibitors targeting this kinase act on the whole cellular pool of the protein and lack organelle selectivity, which drives toxicity and resistance. There is therefore a strong need for molecules that selectively disrupt the mitochondrial protein-protein interaction (PPI) between this kinase and the ATP5F1 complex. Our group has a strong expertise in drug discovery, from in silico drug screening to in vivo evaluation, and in particular in the development of kinase inhibitors and small-molecule PPI modulators.[2,3,4] Building on a first high-confidence structural model of the complex obtained with AlphaFold3 and further evaluated through molecular dynamic simulations, this internship will consolidate the model and exploit it to screen for first-in-class modulators of this interface.
Description of the project & duties – This internship is part of MITOCORE, a collaborative program funded by the Cancéropôle Grand-Ouest, aiming to validate and pharmacologically target the kinase/ATP synthase interaction in breast cancer. You will drive the computational component of the project: refining the structural model of the complex, characterizing its druggable interface, and running a structure-based virtual screening campaign to prioritize candidate modulators for experimental validation by our partner team.
As part of this internship, you will focus on:
- Refining the structural model of the kinase/ATP5F1 interface.
- Running and analyzing molecular dynamics simulations to assess the stability of the complex and to map druggable hot-spots and key interface residues.
- Performing structure-based virtual screening of commercially available, PPI-focused chemical libraries (e.g. ChemSpace, Fr-PPIChem[5]).
- Prioritizing candidate modulators according to predicted binding affinity, binding mode and physicochemical/ADMET properties.
- Preparing a shortlist of compounds and interfacing with the experimental team for split-FAST and biochemical validation.
Main activities and techniques involved –
- Structure prediction and modelling of protein complexes (AlphaFold3, protein-protein docking).
- Molecular dynamics simulations and trajectory analysis (GROMACS, MDAnalysis, etc).
- Analysis of protein-protein interfaces and identification of druggable hot-spots.
- Structure-based virtual screening: compound library preparation, ADMET/physicochemical filtering, docking and candidate prioritization.
- Scientific computing on HPC resources (Eskemm Data mesocentre); Linux environment and scripting (e.g. bash; python).
References:
[1] Sharma et al. Cell Death Discov. 2023, 9, 203. https://doi.org/10.1038/s41420-023-01501-2
[2] Guillory et al. J. Med. Chem. 2020, 63, 6694–6707. https://doi.org/10.1021/acs.jmedchem.9b01942
[3] Pelizzari-Raymundo et al. iScience 2023, 26, 106687. https://doi.org/10.1016/j.isci.2023.106687
[4] Sueron et al. ChemMedChem. 2026, 21, e70385. https://doi.org/10.1002/cmdc.70385
[5] Bosc et al. ACS Chem. Biol. 2020, 15, 1566–1574. https://doi.org/10.1021/acschembio.0c00179.
Where to apply
E-mail: xavier.guillory@univ-rennes.fr
Requirements
Research Field: Chemistry » Computational chemistry
Education Level: Master Degree or equivalent
Skills/Qualifications
Applicant profile – We encourage applications from highly motivated Master/M2 students from the national and international community, with a background in molecular modelling, chemoinformatics, drug discovery, structural biology or related life sciences, and with outstanding qualifications. Familiarity with molecular modelling software, a Linux environment and scripting is appreciated but not required.
Languages: ENGLISH
Level: Good
Additional Information
Benefits
Remuneration: 580€ net/month; Duration: 6 months between January & July 2027
Selection process
Interviews are conducted as I receive applications. The position might be filed before the application deadline if a suitable candidate has been found.
Please send CV, cover letter, M1/4th year transcripts and at least one contact likely to provide a recommendation to:
Dr. Xavier Guillory – xavier.guillory@univ-rennes.fr
DEADLINE – 18th September 2026
Website for additional job details: https://oss-clcc.univ-rennes.fr/
Work Location(s)
Number of offers available: 1
Company/Institute: Inserm U1242 Oncogenesis, Stress, Signaling laboratory
Country: France
State/Province: ILLE ET VILAINE
City: Rennes
Postal Code: 35042
Street: Avenue de la Bataille Flandres Dunkerque, Centre Eugène Marquis, porte D, 1er étage
Contact
City: NANTES
Website: https://grand-ouest.inserm.fr/ https://oss-clcc.univ-rennes.fr/
Street: 24 Boulevard Vincent Gâche
Postal Code: 44200
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