PhD offer in cell Biology (M/F)

Job Description

Thesis Subject

Fibrogenesis is an essential and natural process of extracellular matrix (ECM) remodelling at the core of tissue formation and repair. It is characterised by the synthesis and degradation of extracellular fibrous proteins, primarily collagens. Prolonged tissue damage leads to a deregulation of this physiological process and an abnormal accumulation of ECM proteins, a phenomenon known as fibrosis. Fibrosis is a common pathological feature of chronic diseases and affects millions of people worldwide, representing a major clinical challenge with limited therapeutic options. To alleviate the burden of fibrosis and foster the development of new antifibrotic therapies, a comprehensive understanding of the fibrotic molecular mechanisms is needed. Fibroblasts are the main cells involved in the ECM production. Whilst the key roles of inflammation and Transforming Growth Factor (TGF-β)-dependent signalling have been extensively studied in the context of fibrosis, the impact of the local decrease in oxygen concentration (hypoxia), a common feature of fibrosis, is less well understood. Hypoxia-inducible factors (HIFs) are the master regulators of the cellular adaptive response to the hypoxic environment.

The project aims to investigate the role of HIFs in skin fibroblasts, on the collagen synthesis, maturation and deposition processes. Systemic sclerosis will be used as a disease model, as it is characterised by hypoxia and cutaneous and pulmonary fibrosis. The project aims to elucidate the multiple mechanisms by which hypoxia contributes to collagen deposition in physiological and pathological fibrotic contexts. One of the focus will be to understand the role of hypoxia in the proteolytic maturation of collagen via bone morphogenetic protein 1 (BMP-1). The results will significantly improve our understanding of the balance between healthy fibrogenesis and pathological fibrosis and may open direct translational perspectives for patients with fibrotic diseases.

This project will combine basic research, using biochemical and cell biology techniques, with translational research involving preclinical mouse models and clinical samples. The supervisory team is expert in hypoxia signalling and collagen assembly and will work closely with a team based in Paris, specialists in the molecular understanding of systemic sclerosis and its clinical care.

Prerequisites: a solid knowledge of molecular and cellular biology (Master's level)

Your Work Environment

The PhD project will be carried out at the Institute of Biology and Protein Chemistry (CNRS, Lyon) within the Laboratory of Tissue Biology and Therapeutic Engineering (https://lbti.ibcp.fr/). The supervisory team is part of the MatrHyCut team led by Dr Moali. At the start of the PhD project, the team will comprise 5 academic staff members (3 CNRS researchers, 1 university professor, 1 hospital-based professor), 1 technical support staff member, 1 postdoctoral researcher and 3 PhD students. The student will be co-supervised by Dr Catherine Moali (specialist in collagen assembly) and Prof Violaine Sée (specialist in cellular adaptation to hypoxia). At the start of the project, the student will work closely with a senior PhD student finishing their thesis. The project is fully funded by a national ANR grant aimed at understanding the impact of hypoxia on fibrosis, using systemic sclerosis as a pathological model. This aspect will be carried out in collaboration with Prof. Allanore at Cochin Hospital in Paris.

Constraints and risks

The research is conducted in an organisation hosting sensitive information and critical technologies. It therefore falls in the PPST initiative (Protection of Scientific and Technical Potentials). Therefore, in accordance with the regulations, authorisation from the relevant authority has to be obtained for the selected candidate before the start of the project.

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

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