Postdoctoral researcher

Synthesis of Prussian Blue Nanoparticle / Antimicrobial Peptide Hybrid

Conjugates for Antibacterial Applications

Laboratory of Immunology, Immunopathology and Therapeutic Chemistry (CNRS UPR3572, Strasbourg, France), group “Therapeutic multifunctional carbon and 2D nanomaterials” (led by Dr. Alberto Bianco), under the supervision of Dr. Cécilia Ménard-Moyon Team website &

Institute of Chemistry (CNRS-University of Strasbourg UMR7177, Strasbourg, France), group “Biometals and Biological Chemistry” (led by Prof. Peter Faller), under the supervision of Dr. Vincent Lebrun Team website

 

Project description

The rise of bacteria showing resistance towards several antibiotics is already a threat today, but will become a major issue for public health in the near future. This calls for the development of new antibiotics. Ideally, these new antibiotics should both circumvent the current resistance mechanisms, but should also be more difficult to develop resistance to. For example, an antibiotic targeting only one protein target can become inefficient after only few generations, as a limited number of mutations of that particular target allows it not to be affected by the drug anymore. On the other side of the spectra, some compounds are active by affecting a broader range of targets, but are limited due to a lack of specificity (human cells vs. bacteria for example) or a poor delivery to the pathogens.

In this project, we aim at exploring the potential benefit of combining two of such systems. The first one is an inorganic nanoparticle (Prussian blue nanoparticles), that can deliver high amounts of iron ions to the bacteria, disturbing its metal homeostasis and triggering oxidative stress. The second one is an antimicrobial peptide with the capacity to selectively disturb the bacterial membrane. We expect a synergistic effect between both components, that should increase the effectiveness of the whole system. Indeed, the peptide should endow the system with selectivity for bacteria and improve the penetration of the nanoparticles inside bacteria. Once internalized, the toxicity arising from the release of metal ions should add up to that of the peptide, as they act via different mechanisms.

During this project, we will first synthesize the antimicrobial peptides and Prussian blue nanoparticles. The conditions for the synthesis of the nanoparticles will be tuned to obtain different size, shape, crystallinity and surface charge, and also for doping with bactericidal metal ions.

The nanoparticles will be functionalized through different strategies to allow the conjugation of the peptides. The peptide-functionalized nanoparticles will be characterized by different techniques, including transmission/scanning electron microscopy, X-ray photoelectron, thermogravimetric analysis, X-ray diffraction, UV-Vis-NIR and FT-IR spectroscopy. The biological evaluation of the Prussian blue nanoparticle / antimicrobial peptide hybrid conjugates (compatibility with human cells and activity against Escherichia coli and Staphylococcus aureus) will be performed in collaboration with the biologists of the Laboratory of Immunology, Immunopathology and Therapeutic Chemistry and also with the Laboratory of RNA Architecture and Reactivity in Strasbourg (collaboration with David Lalaouna).

Eligibility criteria

The candidate must have a PhD in chemistry with a strong background in materials chemistry and/or organic synthesis. Experience in the synthesis of nanoparticles and/or peptides, or biological activity assessment would be appreciated.

The candidate must be an independent, well-organized and rigorous person. He / she must have good interpersonal skills. He / she must manage his own research and coordinate the different aspects of the work to meet deadlines. He / she must provide ideas for new research projects, carry out scientific bibliography, compile results for publication in peer-reviewed journals and present the results orally.

He / she should actively participate in laboratory meetings. Strong interest for interdisciplinary research is important.

 

Interested candidates must send a cover letter, a curriculum vitae and the contacts of three reference persons to Dr. Cécilia Ménard-Moyon (c.menard@ibmc-cnrs.unistra.fr) and Dr. Vincent Lebrun (vlebrun@unistra.fr) before 30th June 2024.

Provisional start date: 01/10/2024

Contract for 24 months