Postdoctoral research in structural biology - M/F

Job Description

Missions

The objective of this project is to resolve the structure/activity relationships of Lpp binding to the bacterial cell wall by LdtA,B,C transpeptidases. Cells that lack it have greater membrane permeability and susceptibility to antibiotics due to increased permeability of their outer membrane. Therefore, targeting the binding of Lpp to the peptidoglycan layer is expected to eliminate bacteria in patients.

Activity

1. Conduct research, from experimental design to reporting results:
• Determine the structures of the different L,D-transpeptidases (Ldts) by NMR and/or X-ray crystallography, both alone and in complex with their partners.
• Characterise the Ldt / peptidoglycan / Lpp interactions at the structural level, identifying the surfaces and residues involved in recognition.
• Implement complementary biochemical and biophysical approaches (affinity measurements, kinetics, stoichiometry) to define the determinants of these interactions.
• Validate the structural and biochemical findings in vivo, in particular through the design and analysis of targeted mutants.
• Perform molecular docking studies with substrates and inhibitors, in order to guide the interpretation of the experimental data.
• Characterise the interaction between the Ldts and the inhibitors synthesised by collaborators using a range of biophysical methods.
• Liaise with collaborating teams (chemists, microbiologists) and disseminate the results through publications and conference presentations.
2. Participate in laboratory activities :
• Contribute to the research group's day-to-day operations (logistics, monitoring reagent stocks, tidying up, etc.).
• Participate in the Institute's scientific events and outreach activities.

Your Profil

Skills

1. Core Qualifications
• PhD in Structural biology
• Expertise in protein biochemistry and structural biology (NMR)
• English (written/oral) level B2

2. Technical expertise
• Structural biology: proven expertise in biomolecular NMR (data acquisition, processing, assignment, interaction mapping) or in X-ray crystallography (crystallisation, synchrotron data collection, refinement and validation), together with a good working knowledge of the other approach.
• Protein biochemistry: ability to work independently on heterologous expression (E. coli), multi-step purification and sample quality control; experience in the production of isotopically labelled proteins (¹⁵N, ¹³C) is valued for the NMR part of the project.
• Biophysical characterisation of interactions: hands-on experience with at least two of the following techniques — ITC, SPR, MST, DSF, fluorescence, SEC-MALS — including the quantitative interpretation of binding affinities and stoichiometries.
• Molecular biology: cloning, site-directed mutagenesis and design of expression constructs.
• Computing and modelling: familiarity with the Linux environment and with structural visualisation and analysis software (PyMOL, ChimeraX); a working knowledge of molecular docking and structure prediction (AlphaFold) would be an asset.

3. Behavioral and interpersonal skills
• High degree of autonomy.
• Proactivity and scientific curiosity.
• Open-mindedness and active listening.

Your Work Environment

Located on the Grenoble Science Park (ESRF/ILL/EMBL/IBS), the Institute of Structural Biology (IBS) is a national and international player in the field of integrated structural biology. The IBS is a research center, a technical platform, a host site and a scientific training center. Its mission is to develop research in structural biology, a field of research that is crucial to the understanding of fundamental biological mechanisms. It is supported by 12 state-of-the-art platforms.
As a joint research unit (CEA-CNRS-UGA), the IBS is composed of 20 research groups, each of which proposes a multi-disciplinary approach, at the frontiers of biology, physics and chemistry, in coherence with 3 research axes. Nearly 320 people work there as researchers, PhD students, engineers and technicians in a multicultural and international environment.
The recruited person will join the NMR group which works on the bacterial wall.

Constraints and risks

Without.
The research will be carried out in either French or English, however it is expected that the non-French speaking candidate will strive to learn the basics of French in order to facilitate communication and integration into the laboratory.

Compensation and benefits

Compensation

between 3041 € et 3467 € (according to experience)

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

The research professions