PhD Position M/F at Université Paris-Saclay in Biology, Medicine and Health

Job Description

Thesis Subject

Context:
The Enamel Renal Gingival syndrome (ERS) is a rare disease associated with pathogenic FAM20A alleles. To date, ERS disease ineluctably progresses as no therapy is available to intercept the resulting jaw malformation. The exclusive option is extensive and painful surgery in adults. Only this procedure enables to fit a dental prosthesis providing some relief to the handicaped patients. Furthermore, the natural history of the disease is not defined. The mechanisms leading disease initiation and progression are unclear. There are no molecular tools for diagnosis and prognosis.

The objective:
This PhD project is part of a multidisciplinary research project funded by the French National Research Agency (ANR). It aims to provide an in depth understanding of ERS pathophysiology and implement new diagnosis and treatment tools based on extracellular vesicles (EVs). EVs are very small particles (∼40-160nm) surrounded by a lipid bilayer and carrying a cargo rich in lipids, proteins,
carbohydrates, nucleic acids (DNA, mRNA and miRNA) as well as various growth factors. Y et, the functional role of miRNAs within the EV cargo remains unknown in ERS. The purification and characterization of extracellular vesicles remains a key step for their use as diagnostic markers or as therapeutic agents, which, today , represents a real limitation.

PhD Project Responsibilities:
The successful candidate will be based at the Saclay and Imagine laboratories and will be responsible for:
• Understanding how to produce extracellular vesicles (EVs) from human primary cell cultures, including the maintenance and
expansion of cells under optimized and controlled conditions.
• Isolating and purifying EVs from cell culture supernatants using various established methods such as ultracentrifugation and size-exclusion chromatography .
• Characterizing EVs with advanced analytical techniques available in the laboratory , including Western blotting, dynamic light scattering (DLS), cryo-transmission electron microscopy (cryo-TEM), and nanoparticle tracking analysis (NTA), among others.
• Assessing cellular uptake of EVs in vitro using appropriate cell models. • Evaluating the in vivo biodistribution of EVs following injection into mice.

Profile and skills required
- Basic cell culture especially primary cell culture.
- Knowledge on purification techniques and characterization methods of EVs;
- Hands-on experience in cell biology techniques (e.g. real-time PCR, Western blot, ELISA, immunofluorescence microscopy, Flow cytometry);
- Strong interest for pluridisciplinary research;
- Good communication skills and ability to work in a multidisciplinary team.

Your Work Environment

This PhD project will be carried out primarily at the Institut Galien Paris-Saclay (IGPS, CNRS UMR 8612). As this is a multidisciplinary project, the PhD candidate will also be required to work at the partner institute, the Institut Imagine - Université Paris Cité.
The PhD candidate will be supervised by Dr Mariana VARNA (Université Paris-Saclay; 35% supervision) and co-supervised by Dr Sameh OBEID (Université Paris-Saclay; 35% supervision) and Dr Nunthawan NOWWAROTE (Université Paris Cité; 30% supervision).
At Université Paris-Saclay, the PhD candidate will be responsible for the purification and characterization of extracellular vesicles, as well as part of the in vitro and in vivo evaluations.
At Université Paris Cité, the PhD candidate will be responsible for producing extracellular vesicles from cell lines and will also contribute to part of the in vitro and in vivo evaluations.
Weekly meetings will be scheduled to monitor the progress of the research project. The PhD candidate will give oral presentations to the members of the teams involved and will also present their work during the PhD and Postdoctoral Research Day organised by the Institut Galien Paris-Saclay.
The PhD candidate will have access to the equipment and facilities available at the Institut Galien Paris-Saclay, the IPSIT research platforms (Ingénierie et Plateformes au Service de l'Innovation Thérapeutique, Université Paris-Saclay), and the facilities available at the Institut Imagine (Université Paris Cité).

Constraints and risks

No specific risks. The risks associated with the position are those typically encountered when working in a cell and molecular biology or biochemistry laboratory, and where applicable, in an animal facility, including the handling of biological samples, cell cultures and chemical products. These risks are managed by complying with the applicable health and safety procedures (e.g. use of appropriate protective equipment and work under a fume hood or other suitable containment equipment when required).
Animal experiments will be conducted in authorised facilities, in accordance with the relevant regulatory approvals and the applicable rules on animal research ethics and welfare.
The PhD candidate will be required to comply with the safety instructions and procedures applicable at the IGPS and at the partner site, Institut Imagine–Université Paris Cité. The project will also involve occasional travel between the two sites.

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