PhD student M/F: Development of methods for cryo-EM image analysis and protein docking to elucidate binder-induced conformational changes (PhD cotutelle with mandatory one-year stay at the University of Melbourne)

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Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie

PARIS 05 • Paris

  • FTC PhD student / Offer for thesis
  • 36 mounth
  • BAC+5

This offer is available in English version

This offer is open to people with a document recognizing their status as a disabled worker.

Offer at a glance

The Unit

Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie

Contract Type

FTC PhD student / Offer for thesis

Working hHours

Full Time

Workplace

75252 PARIS 05

Contract Duration

36 mounth

Date of Hire

01/10/2026

Remuneration

2300 € gross monthly

Apply Application Deadline : 08 May 2026 23:59

Job Description

Thesis Subject

This PhD project aims to develop advanced software solutions for cryo-electron microscopy (cryo-EM) data analysis, modeling conformational heterogeneity, and identifying optimal binding candidates, by integrating image analysis and docking across multiple structural states. The new tools will be validated through their application to VCP/p97 data, a key protein that plays a central role in cellular homeostasis by extracting and unfolding damaged or unwanted proteins for their degradation [1]. The project will build on the image analysis software MDSPACE, which produces detailed maps of the conformational states of biomolecular complexes from cryo-EM images [2,3].

MDSPACE will be used to obtain a detailed map of the conformational states of VCP/p97, induced by nucleotide binding and miniprotein engagement. In parallel, a new docking software, MDSPACEdock, will be developed to enable rapid docking of potential ligands across the full conformational ensemble obtained by MDSPACE, rather than a single static structure. This multi-state docking approach will be based on a scoring function combining shape complementarity and approximate binding free energy in order to rank binding candidates while accounting for structural flexibility. By applying MDSPACEdock to wild-type VCP/p97 conformations obtained by MDSPACE from cryo-EM images, the project will identify the main binding candidates as well as their preferred binding conformations, thereby providing mechanistic insight into ligand–VCP recognition.

More broadly, the project will deliver computational tools and workflows for biomolecular conformational analysis by cryo-EM integrated with ligand selection, which will be applicable to other dynamic protein complexes.

Requirements:
‒ Master 2 in computer science, bioinformatics, biophysics, or a related field
‒ Strong theoretical foundations and practical skills in at least two of the following areas: AI/ML, image processing, molecular modeling and docking
‒ Strong experience in Python and C++ programming (knowledge of Fortran is a plus)
‒ Strong interest in interdisciplinary research bridging computer science, physics, and biology
‒ Excellent oral and written communication skills
‒ Strong organizational skills, autonomy, and efficiency
‒ Commitment to quality and rigor in work
‒ Analytical and conceptual skills
‒ Good interpersonal skills and team spirit
‒ Availability for a one-year stay at the University of Melbourne (second year of the PhD). University of Melbourne entry requirements: First Class Honours (H1) or equivalent (~80%; excellent Master 2, top 10%), and English language requirements.

References:

[1] Valimehr S, Sethi A, Shukla M, Bhattacharyya S, Kazemi M, Rouiller I. Molecular Mechanisms Driving and Regulating the AAA+ ATPase VCP/p97, an Important Therapeutic Target for Treating Cancer, Neurological and Infectious Diseases. Biomolecules 2023; 13: 737. https://doi.org/10.3390/biom13050737

[2] Vuillemot R, Mirzaei A, Harastani M, Hamitouche I, Frechin L, Klaholz BP, Miyashita O, Tama F, Rouiller I, Jonic S. MDSPACE: Extracting Continuous Conformational Landscapes from Cryo-EM Single Particle Datasets Using 3D-to-2D Flexible Fitting based on Molecular Dynamics Simulation. J Mol Biol. 2023;435:167951. https://hal.science/hal-03929029

[3] Valimehr S, Vuillemot R, Kazemi M, Jonic S, Rouiller I. Analysis of the Conformational Landscape of the N-Domains of the AAA ATPase p97: Disentangling the Continuous Conformational Variability in Partially Symmetrical Complexes. Int J Mol Sci. 2024;25. https://hal.science/hal-04519643

Your Work Environment

The PhD student will be co-supervised by a researcher from Sorbonne University (regarding the computational method development) and a researcher from the University of Melbourne (regarding the application of the new methods to VCP/p97 data). This is a joint PhD thesis between Sorbonne University and the University of Melbourne, with a mandatory one-year stay at the University of Melbourne (during the second year of the PhD). At Sorbonne University, the student will join IMPMC-UMR 7590 (https://impmc.sorbonne-universite.fr/en). At the University of Melbourne, the student will join the Bio21 Molecular Science & Biotechnology Institute (https://www.bio21.unimelb.edu.au).

As this is a joint PhD program between Sorbonne University and the University of Melbourne, candidates must meet the doctoral admission requirements of both universities. For international applicants to the University of Melbourne, this generally corresponds to a very high academic level (often around 80% of the maximum grade, or equivalent depending on the grading system). In the French system, this generally corresponds to an excellent Master 2 performance, ranking among the top 10% of the class.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

Offer reference UMR7590-SLAJON-008
CN Section(s) / Research Area Information sciences: processing, integrated hardware-software systems, robots, commands, images, content, interactions, signals and languages

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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PhD student M/F: Development of methods for cryo-EM image analysis and protein docking to elucidate binder-induced conformational changes (PhD cotutelle with mandatory one-year stay at the University of Melbourne)

FTC PhD student / Offer for thesis • 36 mounth • BAC+5 • PARIS 05

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