PhD : Molecular mechanism of the multidrug ABC Transporter BmrA(M/F)

Job Description

Thesis Subject

Scientific Context : Multidrug resistance (MDR) in bacteria is a major global health threat, compromising the effectiveness of antibiotic treatments. Polyspecific drug transporters are key players in bacterial resistance, enabling the efflux of a wide range of antibiotics out of the cell. BmrA, an ATP-Binding Cassette (ABC) transporter, serves as a model system to investigate these mechanisms.

One key question is how BmrA can efflux a vast range of drugs and, in particular, does the resting state require a wide-open conformation to accommodate the largest molecules? In addition, it is known that different drugs can bind simultaneously to the transporter and trigger a cooperative transport mechanism, but this cooperativity remains poorly understood.
This project is funded by the ANR-DFG (a bilateral French-German collaboration) and aims to address these questions using a multidisciplinary approach, combining molecular biology (e.g. site-directed mutagenesis; membrane protein production and purification (overexpression and purification of wild-type (WT) and mutant BmrA); functional characterization (ATPase activity assays; drug transport assays; drug-binding studies (e.g., Isothermal Titration Calorimetry, fluorescence-based assays); structural biology (cryo-electron microscopy to determine the 3D structures of WT and mutant BmrA).
Candidate Profile : We are seeking a highly motivated PhD candidate with a strong background in biochemistry and a keen interest in structural biology and biophysics. Experience with or knowledge of membrane proteins and structural biology techniques would be an advantage. The candidate should be curious, enthusiastic about research, and motivated to investigate membrane proteins at the interface of biochemistry, structural biology, and biophysics.
Application Process : Candidates should submit a CV and a cover letter outlining their research interests and motivation. Please also include the names and contact details of two referees. Contacts : jean-michel.jault@ibcp.fr and cedric.orelle@ibcp.fr

P.S. This PhD position corresponds to the one we recently posted on LinkedIn. If you have already applied and your application was not retained because your profile did not match our requirements, please do not apply again.
Relevant publications from the laboratory :
• Di Cesare et al. (J. Biol. Chem. 2024). The transport activity of the multidrug ABC transporter BmrA does not require a wide separation of the nucleotide-binding domains.
• Pérez Carrillo et al. (Nat. Commun. 2025). Bidirectional communication between nucleotide and substrate binding sites in a type IV multidrug ABC transporter

Your Work Environment

Research Environment : Host laboratory: Molecular Microbiology and Structural Biochemistry (MMSB) research unit, Lyon Gerland Biosciences Campus. Joint unit under CNRS and University of Lyon 1 supervision. Research focus: Understanding the molecular mechanisms of microbial pathogenesis and macromolecular interactions (structure, dynamics, and function).
Work environment : Located near Lyon city center, with easy access to public transportation (metro, tram, bike lanes). State-of-the-art facilities and a supportive, collaborative atmosphere. Opportunities for training, conferences, and international collaborations (e.g., with German partners in the ANR-DFG project).

Constraints and risks

None

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

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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