Description du sujet de thèse

Amyloid proteins are widespread in nature, from humans to bacteria, and are characterized by their ability to aggregate into ordered fibrils. Historically associated with neurodegenerative diseases (e.g., Alzheimer's), they have more recently been identified in the context of bacterial infectious diseases. To date, no consensus has emerged regarding the role of certain amyloids, specifically the phenol-soluble modulins (PSMs) secreted by Staphylococcus aureus, in biofilm architecture, particularly their role in bacterial adhesion within biofilms.
This PhD project aims to characterize the molecular interaction forces involved and to identify the active entities responsible for intercellular adhesion and bacterial anchoring to substrates, ultimately to understand how PSMs modulate biofilm formation and detachment. To achieve this, the candidate will primarily utilize atomic force microscopy (AFM) in single-cell force spectroscopy (SCFS) mode: a single living cell will be attached to the tip of an AFM cantilever and brought into contact with a substrate or another cell to quantify adhesion forces. Given that biofilms can form on various surfaces, different substrates—hydrophobic, hydrophilic, or coated with proteins of interest—will be tested. PSMs in different forms (α or β, monomers to fibrils) will then be introduced, and interactions will be reassessed.

By analyzing the evolution of adhesion forces and their frequency, this study aims to determine whether PSMs act as "promoters" of adhesion, ultimately enhancing biofilm resistance, or as "inhibitors" of adhesion, ultimately facilitating biofilm detachment. To ascertain whether the effect of PSMs is purely extrinsic, bacterial strains that naturally produce these peptides will be compared with genetically modified strains lacking PSM expression. This single-cell study will be complemented by ensemble experiments on biofilms. Fluorescence microscopy will be used to analyze biofilm architecture before and after PSM treatment, potentially correlating the findings with their morphological and mechanical properties as measured by AFM. Lastly, special attention will be given to multi-species biofilms to assess the impact of PSMs not only on the adhesion of PSM-producing bacteria but also within more complex interspecies communities competing for ecological niches of clinical relevance.

Contexte de travail

The "Methodological Developments in AFM for Biology" group at CBMN (Bordeaux) is currently seeking a motivated PhD candidate to study the role of bacterial peptide self-assemblies in the structuring and dissemination of biofilms. This interdisciplinary project, funded by an ERC StG 2024 grant, lies at the crossroads between microbiology, biophysics, and chemistry.
The selected candidate will work within the CBMN, which provides a dynamic and stimulating environment to tackle major challenges in the field of amyloids and their functional roles in bacteria. More specifically, the candidate will join a team of experts in AFM, recognized for their expertise in bacteriology and the biophysical characterization of amyloid proteins. Additionally, the candidate will benefit from a collaborative network of experts in cellular and molecular biology, physical chemistry, and cutting-edge methodological developments.
Given the interdisciplinary nature of the project, we are seeking a highly motivated candidate with a degree in microbiology, biophysics, or physical chemistry. A strong interest in interdisciplinary approaches, as well as in exploring and combining advanced methodologies to elucidate the structure-function relationship of bacterial functional amyloids, will be highly valued. Prior experience in (i) bacterial cell culture, (ii) biomolecule manipulation (proteins/lipids), or (iii) fluorescence microscopy and/or atomic force microscopy will be considered an asset. Finally, we are looking for a proactive and independent candidate with strong organizational and communication skills, capable of working effectively within a team.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.