Offre de thèse co-supervisée entre les laboratoires AFMB et LCB

Study of PilY1, ubiquitously found at the tip of bacteria pili: biology, regulated assembly and adhesion properties

Keywords

Type IV Pili, motility, adhesion to sugar and proteins, nanomachines, development

Summary

Type Four Pili (T4P) are exceptionally widespread bacterial nanomachines that mediate a variety of functions, including motility, infection and competence1. T4P share a universal feature, which is the ability to adhere to substrates. The binding to substrates is ensured by proteins termed PilY1 and located at the tip of the pilus fiber 2,3. While in known bacterial pathogens, such as Neisseria sp and Pseudomonas aeruginosa, PilY1 homologs are essential for the adhesion to host cells and infection, in the soil bacterium Myxococcus xanthus, PilY1 proteins are essential for cell-group motility and fruiting body formation. M. xanthus T4P can be accessorized by one of two distinct PilY1 proteins, predicted to bind each to a different ligand, PilY1.1 to sugars and PilY1.3 to proteins, and whose assembly is modulated at a transcriptional and post-translational level2,3. The presence of two PilY1 homologs with different binding specificity makes M. xanthus an interesting model for characterizing the exact role of these proteins in complex social behaviors and their functional diversification. With this thesis project, we aim to characterize the exact role of each PilY1 homolog in specific cell group behaviors including social motility and fruiting body formation; determine the regulatory mechanisms governing the differential assembly of PilY1 proteins; characterize the sugar or protein binding specificities of each PilY1 homolog and determine the impact of such binding on cell behaviors.
This is an ambitious project combining in vivo and in vitro complementary approaches. The two supervisors, Emilia Mauriello (S1) and Renaud Vincentelli (S2) have recognised expertise in all the aspects involved and the student will benefit of recently developed and advanced approaches: high-throughput protein purification, interaction and refolding (S2), in vivo dynamics of the pilus fibers (S1), protein-protein/sugar interaction (S2), M. xanthus cell biology and microscopy (S1).
The characterization of the tip proteins of other bacterial appendages has led to the development of specific treatments for infections mediated by these structures4. In the case of T4P, the regulation mechanisms governing the assembly of PilY1 proteins, the correlation between binding specificity and bacterial ecology, as well as the nature of the ligands remain mostly elusive despite their conservation and significance in bacterial infections. The study of PilY1 proteins may facilitate the development of antimicrobial treatments specifically targeting T4P adhesion.

1. Pelicic, V. Microbiology (Reading) 169, 001311 (2023).
2. Xue, S. et al. Mauriello, EM. PLoS Genet 18, e1010188 (2022).
3. Treuner-Lange, A. et al. Nat Commun 11, 5054 (2020).
4. Hatton, N. E., Baumann, C. G. & Fascione, M. A. Chembiochem 22, 613–629 (2021)
5. Vincentelli R, Luck K et al, Nat Methods. 2015 Aug;12(8):787-93. * equal contribution
6. Gogl G et al. Nat. Commun. 2022 Dec 7;13(1):7555

The co-supervisors
Emilia Mauriello, Laboratoire de Chimie Bactérienne – LCB, emauriello@imm.cnrs.fr, https://lcb.cnrs.fr/team/pelicic/
Renaud Vincentelli, laboratoire Architecture et Fonction des Macromolécules Biologiques – AFMB, renaud.vincentelli@univ-amu.fr, https://www.afmb.univ-mrs.fr/en/facility/structural-biology/high-throughput-cloning-expression-in-bacteria-purification-and-interaction-of-recombinant-proteins/, https://www.afmb.univ-mrs.fr/en/team/viral-macromolecular-complexes/

Location
LCB (https://lcb.cnrs.fr/) and AFMB (https://www.afmb.univ-mrs.fr/), respectively Campus Joseph Aiguier and Luminy campus, Marseille, France

Doctoral school
Life Sciences (ED 658), Aix-Marseille université (https://ecole-doctorale-658.univ-amu.fr/fr)

Expected profile of the candidate
The ideal candidate should have some background in molecular biology and biochemistry. The microscopy, high-throughput purification and hold-up assays 5,6 will be acquired throughout the PhD program. Familiarity with some principles of microbiology and gene regulation is highly desirable. The candidate should be highly motivated, independent, and comfortable working in team and in an interdisciplinary research environment combining in vivo and in vitro approaches.

How to apply?
Send us a CV (specifying the English level), a cover letter, transcripts and ranking of Master degree (Master 1 and first semester of Master 2), and the contact information for at least two references by May 30th 2025.
Emilia Mauriello, (LCB), emauriello@imm.cnrs.fr
Renaud Vincentelli, (AFMB), renaud.vincentelli@univ-amu.fr
The candidate selected by the co-supervisors will be interviewed on July 7th 2025 by the Institute of Microbiology, Bioenergies and Biotechnology (IM2B) jury. Defense modalities will be given later.