Offer

Team: Viral Replicases – Structure, Mechanism, and Drug Design
PhD Start: Early 2026
Funding: AMIDEX / BPI France (secured, 3 years)
Workplace: AFMB (Architecture and Function of Biological Macromolecules), Luminy Campus, Aix-Marseille University, CNRS – Marseille, France

PhD Topic: Development of New Technologies for Therapeutic and Vaccine RNA Synthesis

Project Objectives and Content: This PhD project focuses on the design of innovative therapeutic RNAs capable of closely mimicking cellular RNAs and is part of a collaborative project with an industrial partner. The project includes:

  1. Directed evolution experiments on enzymes to improve their catalytic properties and generate new tools transferable to industry.
  2. Evaluation of the impact of introduced modifications on RNAs (in collaboration with a team from CIML), particularly regarding innate immune activation and the efficacy of the corresponding therapeutic products.

This project, at the interface of academic research and industrial development, offers a multidisciplinary environment integrating structural biology, enzymology, cell biology, and immunology. It will be carried out in close collaboration with a research engineer responsible for developing the necessary methodologies and tools, as well as a PhD student in the final stage of their thesis.

Project Summary: The project aims to develop optimized and engineered polymerases to enhance their efficiency and stability in the synthesis of therapeutic and vaccine RNAs, with a particular focus on phage RNA polymerases.

The approach is based on engineering polymerase mutants capable of incorporating modified nucleotides and initiating synthesis in the presence of short RNAs carrying cap analogs. Individual mutations have already been identified in various polymerases, and we will combine this information with structural knowledge of the polymerases to target critical regions for synthesis initiation.

The host team, recognized for its expertise in viral replication mechanisms, polymerase characterization, and inhibitor identification, has also demonstrated how viruses modify their RNAs via methylations to evade cellular defenses.

By combining these skills in polymerase engineering and RNA modification processes (capping and methylation), our strategy is to develop an innovative procedure that can significantly improve therapeutic and vaccine RNA synthesis technologies.

Skills and Qualifications: The candidate must hold a Master’s degree (or equivalent) in Molecular Biology, Biochemistry, Structural Biology, or Biotechnology, with a minimum final grade of 12/20.
Experience in RNA biology, biochemistry, or protein purification will be highly appreciated.

The PhD will be carried out at Aix-Marseille University within Doctoral School 658:
https://ecole-doctorale-658.univ-amu.fr/
Eligibility for enrollment will be assessed by Doctoral School 658.

Application Procedure: Candidates are invited to send a CV and a cover letter to: etienne.decroly@gmail.com
Etienne Decroly, laboratoire AFMB, 13009 Marseille (ORCID : 0000-0002-6046-024X).

Published on October 23, 2025