Role of the lysosome and impact of the protein corona in the lung toxicity of nanoparticles
With the development of nanotechnologies, more and more nanoparticles (NPs) are being developed for industrial or biomedical applications. Our team is working on the design of NPs for drug delivery and biomedical imaging (theranostic NPs). This research focuses on the lung and includes toxicological studies in order to design safe NPs. Indeed, NPs could have undesirable cellular and tissue effects. Among other, after entering the cell, NPs accumulate in the lysosomes, where they trigger a loss of integrity of the lysosome resulting in the release into the cytosol of proteases and protons responsible for oxidative stress and activation of the NLRP3 inflammasome. In biological fluids, the NPs are rapidly covered with proteins forming what is called the “protein corona”. The characteristics of the NPs (composition, charge, surface chemistry) determine the identity of this corona. Conversely, the identity and fate of this corona can affect the way the NPs interact with the cells and the lysosome.
In this context, the objective of the research project to which the recruited person will join, is to study the interaction of NPs with lysosomes, the role of the protein corona in this interaction, and the toxicological consequences of this interaction in the lung. This project, financed by the ANR, is developed in the UMR 7199, based at the Faculty of Pharmacy, on the Illkirch campus (Strasbourg University). It focuses on carbon NPs, called carbon dots, developed by the laboratory for drug delivery applications. It consists in studying: 1-the ability of these NPs to adsorb proteins on their surface and the fate of the protein corona under lysosomal conditions, 2-the trafficking of these NPs to lysosomes, 3-the effect of these NPs on lysosomal integrity and function in in vitro (macrophages) and in vivo (normal mice and mouse model of asthma) models, and 4-the effect of these NPs and the involvement of the lysosome in the allergen response in vitro (dendritic cells).
The candidate should have a good background in cellular and molecular biology and knowledge of physiology/physiopathology. Knowledge of proteomic approaches would be a plus. He/she should have a strong interest in research at the interface of life sciences and chemistry. The multidisciplinary aspect of the project (physicochemical analysis of particles, in vitro and in vivo studies, toxicology) and the expertise of the team in these different fields constitute an important asset for the young researcher and his/her opening to research areas at the chemistry-biology interface in the field of drugs.
Position type: Post-doctoral
Starting date: December 1, 2021
Project duration: 1 year
Technical skills: proteomic analysis; cell culture; cytotoxicity assays (viability, lysosomal integrity and function, autophagy, inflammation); electrophoresis and western blotting; flow cytometry; confocal microscopy.
Applications (CV, covering letter and letters of recommendation) to be sent by e-mail to:
Françoise Pons (email@example.com) & Carole Ronzani (firstname.lastname@example.org)
Laboratoire de Conception et Application de Molécules Bioactives – UMR 7199 CNRS-Unistra Équipe “Vecteurs : Synthèse, Applications & Toxicologie”
Faculté de Pharmacie, 74 route du Rhin, F-67401 Illkirch https://camb.cnrs.fr/vsat/