Tissue Tropism of Staphylococcus aureus in Sepsis (M/F)

Job Description

Thesis Subject

Staphylococcus aureus is responsible for approximately 25% of nosocomial infections in France and is the leading cause of death from nosocomial infections, with mortality rates reaching 40% in cases of multi-organ complications (severe sepsis, endocarditis) (APM News; Deniau et al., 2020). However, the molecular mechanisms underlying its tissue tropism (liver, lungs, kidneys, endocardium) remain poorly understood, which hampers the development of targeted therapies.
The project aims to:
- Identify omics signatures (genetic, epitranscriptomic, proteomic) associated with tissue tropism, through the initial analysis of 300 clinical isolates from patients with various pathologies.
- Validate these mechanisms in murine models of systemic infection to confirm their relevance in vivo.
- Correlate molecular profiles with clinical severity to propose prognostic biomarkers and innovative therapeutic targets.

Your Work Environment

The PhD student will be integrated into the Institute for Integrative Biology of the Cell (I2BC), a joint research unit (UMR 9198) under the supervision of the CNRS, Université Paris-Saclay, and the CEA. The I2BC is a dynamic scientific environment dedicated to the study of cellular and molecular mechanisms. The project is led by the IHU PROMETHEUS in collaboration with several academic and clinical partners. This project adopts a translational approach, combining omics analyses (genomics, epitranscriptomics, proteomics) and experimental models to identify new biomarkers and therapeutic targets. The PhD student will be supervised by a team of experts in bacterial genomics and molecular biology.

Resources: Access to cutting-edge technological platforms (high-throughput sequencing, mass spectrometry) and clinical databases.
Collaborations: The project involves partnerships with hospitals (for access to clinical isolates), offering a collaborative and applied dimension to the research.

Candidate Profile:
The candidate must hold a Master's degree in microbiology, molecular biology, or a related field, with proven experience in the following areas:
- Handling Class 2 pathogens: Experience in L2 laboratories and knowledge of biosafety best practices for handling pathogenic strains (ideally Staphylococcus aureus or other pathogenic bacteria).
- Bacteriology: Proficiency in bacterial culture techniques, phenotypic and genotypic characterization, and pathogenicity analysis methods.
- Mutant construction: Confirmed experience in genetic modification (transposition, homologous recombination, etc.) for functional gene studies.
- Omics data analysis: Skills in bioinformatics (R, Python, genomic/transcriptomic analysis tools) for processing large datasets.
- English proficiency: Fluent in spoken and written English (scientific writing, presentations, international collaborations).
- Teamwork: Ability to thrive in a multidisciplinary environment (biologists, bioinformaticians, clinicians) and actively contribute to collaborative projects.
- Project management: Ability to organize work, meet strict deadlines, and report progress within the framework of collaborative deliverables.

Constraints and risks

Handling of Pathogens:
The project involves the manipulation of Staphylococcus aureus, a Class 2 pathogen. Experimental work will be conducted in a Biosafety Level 2 (L2) laboratory, in compliance with current regulations.
Work with Clinical Samples:
Access to clinical bacterial strains requires strict adherence to biosafety procedures and ethical guidelines (ethics committee approvals, data anonymization).
Management of Omics Data:
The project generates large volumes of data (genomics, transcriptomics, proteomics). Their storage, analysis, and sharing must comply with data protection standards (GDPR for associated human data) and bioinformatics best practices (reproducibility, traceability).
Deadlines and Scientific Pressure:
The project operates within a collaborative and competitive framework, with intermediate deadlines (deliverables for clinical and industrial partners). Strong organizational skills and the ability to work in a team will be essential to meet the set objectives.
Work in a Regulated Environment:
Certain project steps may be subject to administrative constraints (approvals for the use of pathogenic strains, access to facilities).

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions