Chemical biology approaches to rare earth toxicology in Humans
Recent technological developments have expanded and intensified the use of lanthanides in domains as diverse as renewable energy, computing, and medicine. Increasing usage of these metals raises the question of their impact on the environment and human health. However, the potential toxicity of these metal ions, and its underlying molecular mechanisms, are still little known and rarely investigated in human cell models. The goal of the PhD will be to investigate the human cells response to exposure to Ln ions, and to systematically identify the proteins involved in this response, using a set of chemical and biological tools. In particular, we want to address the following questions: which protein networks are activated or deactivated following Ln exposure? Do Ln ions affect phosphorylation of proteins? Which proteins are directly interacting with Ln ions? will thus decipher what are the key biological interactors of lanthanides, their roles in living systems and the features that enable efficient binding to metals. We expect that our findings will give insights into the toxicology of those elements and inform environmental and occupational safety policies. On the longer term, new bio-inspired strategies for their extraction, recycling, decorporation and remediation will arise from the molecular understanding of metal-life interactions, enabling a well thought-out usage of these elements to support the environmental and numerical transitions.s
Ultra-fast pathogenic bacteria detection in human blood
This project aims to develop a versatile and easy-to-use surface plasmon resonance imaging (SPRi) instrument for the rapid and broad-spectrum detection of low concentrations of pathogenic bacteria in complex samples, particularly blood. SPRi is a label-free technique that allows real-time probing of a sample (regardless of its optical transparency). Due to the high sensitivity of the plasmon phenomenon, the dynamic range of measurable index variation is limited by SPRi detection when reading is performed at a fixed angle, as is the case in commercially available devices. This reduces the use of such optical instruments to the study of environments whose index remains relatively stable during the experiment and whose molecular probes have molecular weights comparable to the targets (monitoring of bimolecular interactions).
This considerably limits the detection of growing bacteria in complex environments. Our laboratory has developed original solutions for the detection of very low levels of contamination in food matrices (creation of a start-up in 2012), but SPRi is unsuitable for the detection of bacteria in blood, partly due to the very high intrinsic variability of this matrix.
These limitations will be overcome by integrating five complementary components:
1. The design of an instrument optimized for real-time recording of SPR images over a defined range of illumination angles;
2. The development of dedicated SPR data analysis and processing to extract the most relevant information for each probe from the images in real time;
3. The functionalization of biochips through a combination of appropriate probes (series of peptides such as antimicrobial peptides (AMPs), antibodies, and even bacteriophages) to optimize the number of possible identifications with a reduced set of probes;
4. The learning of specific “4D-SPRi signatures” of model strains in blood matrices;
5. Validation of the performance of the new “4D-SPRi” instrument as a tool for detecting and characterizing bacteria from hospital strains compared to reference techniques.