Description du sujet de thèse

The objectives this job will be (i) to investigate the immunomodulatory properties of extracellular vesicles for fistulizing Crohn's disease ; and (ii) to compare the immunomodulatory properties of vesicles produced by different methods.
The work will be performed in 2 parts :
A) Development of the potency assays
- Culture of a human colon adenocarcinoma cell line and an immortalized human colon cell line
- Measurement of their production of pro-inflammatory cytokines using multiplexe electrochemiluminescence dosing (basal production versus production after TNFα stimulation)
- Fine-tuning of the optimal stimulation protocol and optimal control conditions

B) Comparison of the effect of vesicles produced by different methods on the production of pro-inflammatory cytokines by TNFα-activated human colon cells using multiplexe electrochemiluminescence dosing
.
Activities :
Recent evidence from our team showed the promising potential of extracellular vesicles (EVs) produced from adipose-derived mesenchymal stromal cells (ADSCs) in this indication. EVs are membrane-bound subcellular entities (40-5000nm) containing proteins, lipids and nucleic acids secreted by the cells in a constitutive or induced manner.
It has been shown before that the cargo of EVs is strongly dependent on their production process, with potential impact on their therapeutic properties. Therefore, there is a stringent need to develop reliable in vitro potency assays to compare the properties of different batches of EVs and predict their therapeutic effect in vivo. These will be the main activities of this thesis which will also focus on EVs from bacteria in a comparative approach

Competences
Cellular culture
Characterization of vesicles by nanoparticle tracking analysis and protein assay
In vitro potency tests

Expertise (at least 6 months) in the characterization of extracellular vesicles is absolutely required
Experience in vesicle potency testing is absolutely required

Contexte de travail

The laboratoire Matière et Systèmes Complexes (MSC) (http://www.msc.univ-paris-diderot.fr/) is a joint unit of the University of Paris (faculty of sciences) and the CNRS bringing together 160 researchers, teaching researchers and technical staff, students, postdoctoral researchers and apprentices) develops interdisciplinary physics, in contact with chemistry, life sciences and medicine. Several large-scale projects around nano-medicine, morphogenesis, control of living organisms, cellular therapies, mechanobiology and extracellular vesicles are thus developed at the MSC laboratory, in very strong interaction with numerous biologist and chemist partners and doctors.
The MSC-Med branch of the MSC laboratory (University of Paris/CNRS), dedicated to the physics/medicine/innovation interface, was created in 2018 on the Saint Germain campus (rue des Saints Pères)(700 m2). In order to better respond to the economic challenges of translational research, from the bench to the patient, MSC-Med goes beyond a fundamental bridge between physics and medicine and offers a pilot space, which opens up to the world socio-economic and which revisits the interaction between research laboratory, students and entrepreneurs. MSC-Med is an original research tool, bringing together around twenty physicists, doctors, pharmacists, biologists, engineers, entrepreneurs, students around the engineering of life and medicine combining research, training, innovation activities, and entrepreneurship by an original organization dedicated to exchanges between researchers, students and start-ups around biotechnologies for health.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.