PhD position at the Enzyme and Cell Engineering Lab, Amiens, France

Three-year PhD position at the Enzyme and Cell Engineering Lab, Amiens, France

Title : Unveiling the mechanism of action of penetrating peptides of the Tachyplesin family against recalcitrant intracellular infections

 

Scientific context

The interest in molecules that can penetrate infected cells and reach intracellular targets - bacteria, viruses, parasites, or even organelles - is growing rapidly due to their applications in difficult-to-treat diseases such as recalcitrant nosocomial infections or cancer, among others. Nosocomial infections are the direct cause of 4,000 deaths each year in France, with a harmful financial impact on the healthcare system 1,2.

Legionella pneumophila, Salmonella typhimurium, and Mycobacterium tuberculosis are well-known examples of difficult-to-target intracellular pathogens. Similarly, bacteria that are generally extracellular, such as Staphylococcus aureus, Escherichia coli,or Pseudomonas aeruginosa can also grow intracellularly, some forming biofilm-like structures inside host cells, leading to difficult-to-treat recalcitrant infections 3,4.

Many varied strategies are under development to target the intracellular pathogen without harming the host cell. One of these strategies is the use of antimicrobial cell-penetrating peptides (ACPPs), a subtype of antimicrobial peptides (AMPs). AMPs are small proteins with potent antiviral, anticancer, antifungal, antiparasitic, and bactericidal properties 5. They are produced by almost all existing organisms and have gained attention due to their low propensity to induce resistance in their target 5,6. Due to their ability to penetrate cells, some AMPs have demonstrated greater efficacy for killing various intracellular organisms than conventional antibiotics 5, whose intracellular concentrations are lower 6. 

Research project

The doctoral thesis project aims to decipher the molecular mechanism by which ACPPs effectively kill intracellular bacteria (such as S. aureus, E. coli, and S. typhimurium) in order to refine their properties for pharmacological applications. During this project, the doctoral student will focus on a series of peptides from the Tachyplesin family to track their penetration properties using NMR and molecular dynamics techniques, among others. In addition, the collaboration of the GEC with other research teams in the region and internationally will allow the student to learn and use more advanced structural biology techniques, as well as state-of-the-art tissue studies (i.e., DNP-NMR, organ-on-chip).

 

The lab

Research at the GEC laboratory focuses on cell biochemistry in plants and animals. Transdisciplinary by nature, it combines experience in the preparation of biological membranes with expertise in NMR and computational methods to study the structure and dynamics of biomolecules (all-atom and coarse-grained molecular dynamics, docking, free energy simulations, and software development). Involved in the study of AMPs for several years, GEC hosts the ADAPTABLE database of AMPs. It has privileged access to the high-performance computing platforms in Amiens and Reims (more than 4000 CPU computing cores, 300 GPUs, 500 teraflops). The group has access to molecular biology, electron microscopy, greenhouse and analytical platforms. In the latter, MS (LC/MS, GC/MS and MS/MS) and NMR (300, 400, 500 and 600 MHz with auto-sampler) instruments are available.

 

Living in Amiens

Amiens, the capital of Picardie, is one hour away from Paris and Lille by train. University students represent more than 25% of its population of 140,000, accounting for a rich cultural life and lively atmosphere. It hosts one of the largest university hospitals in France, powering cutting-edge medical research. Home to the largest gothic cathedral in France (a UNESCO world heritage site) and famous floating gardens, its situation in the Somme valley (with more than 200 km of cycling paths) and the vicinity of the Somme bay (ranked amongst the world’s most beautiful bays) also make it ideal for nature lovers.

 

Eligibility

Successful candidates should hold a Master’s degree (or equivalent) in chemistry, physics, molecular biology or related disciplines and possess an intermediate level of English. Knowledge or experience in NMR and molecular dynamics will be considered a plus.

 

How to apply

Applications should be sent to Francisco Ramos Martín (francisco.ramos@u-picardie.fr) and Nicola D’Amelio (nicola.damelio@u-picardie.fr) before June 1st, 2024, comprising:

  • a curriculum vitae detailing the completed university courses;

  • grades and ranking sheets for the courses followed during bachelor’s and master’s degrees;

  • a letter of motivation in which the candidate advertises her or his suitability to the project;

  • the contact details of at least two of the candidate’s previous supervisors or lecturers willing to recommend their application.

The selected candidate will be required to participate in a competitive selection process between applicants to PhD projects shortlisted by the doctoral school; it is therefore essential that the application file be of high quality. The PhD position will start in October 2024.

 

References

1. Oliveira, R. M. C. et al. Estimating the savings of a national project to prevent healthcare-associated infections in intensive care units. J. Hosp. Infect. 143, 8–17 (2023).

2. Freitas, A. R. & Werner, G. Nosocomial Pathogens and Antimicrobial Resistance: Modern Challenges and Future Opportunities. Microorganisms 11, 1685 (2023).

3. Mirzaei, R. et al. The importance of intracellular bacterial biofilm in infectious diseases. Microb. Pathog. 147, 104393 (2020).

4. Buccini, D. F., Cardoso, M. H. & Franco, O. L. Antimicrobial Peptides and Cell-Penetrating Peptides for Treating Intracellular Bacterial Infections. Front. Cell. Infect. Microbiol. 10, 612931 (2020).

5. Li, J., Wen, Q., Gu, F., An, L. & Yu, T. Non-antibiotic strategies for prevention and treatment of internalized. Front. Microbiol. 13, 974984 (2022).