Missions

The proposed fundamental studies aim to deepen our understanding of autophagy in healthy and pathological contexts. Beyond that, the data acquired in vivo in mice and ex vivo on patient cells should lead to a transfer to clinical applications in the context of MASH and obesity. The immunomodulatory peptide developed in Strasbourg and used in this project is already under evaluation in phase III clinical trials in patients with lupus. In this context, it has shown no harmful side effects in the hundreds of lupus patients who have received the therapeutic peptide. The MASH-Flow program's sustainable and innovative challenges are to reposition this therapeutic peptide in the context of chronic liver diseases. The goal is to slow its severity and prevent MASH from progressing to liver fibrosis or even cirrhosis, with a risk of liver cancer.

Activités

Metabolic dysfunction-associated steatohepatitis (MASH) is a major global health challenge due to its strong correlation with obesity, diabetes, and cardiovascular disease. This serious chronic liver disease affects approximately 4-6% of the global adult population. Current treatments, including lifestyle changes and therapies targeting inflammation and fibrosis, have shown limited efficacy. The MASH-Flow project aims to offer an innovative therapeutic option by simultaneously targeting autophagy, metabolic imbalance, and hepatic stress. The consortium believes that triple therapy, combining new resveratrol derivatives with a caspase-2 inhibitor and an autophagy modulator, will have a synergistic effect in slowing the progression of MASH. Our results in Strasbourg show that the therapeutic peptide that will be used, which targets chaperone-mediated autophagy, blocks the migration of pro-inflammatory cells to inflamed organs and, on its own, slows the progression of MASH in mouse models. This work will be extended and supplemented by studies involving the two other proposed molecules.

Compétences

Advanced skills with autonomy in molecular biology (RT-qPCR), cell biology (murine and human cell culture, flow cytometry), immunochemistry (western blotting, ELISA, antibody purification by affinity chromatography), biochemistry (test of liver markers), work on small molecules (handling and labeling), microscopy (fluorescence, confocal, SEM, histology and immunohistology; tissue sectioning), mass spectrometry and GC/MS, development, work on animal models (injections/blood sampling, dissections including brain; experimentation authorization in France/Europe is mandatory; animal welfare), bioinformatics skills desirable; complete mastery of statistical analyses. Writing reports and articles, internal and external oral/poster presentations, scientific and dissemination of research findings; excellent French/English skills required; supervision of master's students. Ability to work in a team, collective tasks within the team.

Contexte de travail

The candidate (m/f) will work in the Neuroimmunology and peptide therapy team, within UMR7242, located at the Institute of Supramolecular Science and Engineering (ISIS), 8 Allée Gaspard Monge, 67000 Strasbourg Campus Esplanade. The Unit has about 110 people who carry out research on cell signaling pathways and the development of therapeutic strategies. The website of the team in biology is: https://bsc.unistra.fr/recherche/les-equipes-de-recherches/neuroimmunologie-et-therapie-peptidique-pr-sylviane-muller-pr-philippe-georgel/. The team consists of about 7 people.
The MASH-Flow program is supported by the French National Research Agency (ANR) for a period of 48 months. It is a multidisciplinary project that combines the expertise of several CNRS, INSERM, and INRAE laboratories located in Strasbourg (Sylviane Muller), Reims (Sébastien Blaise and Eric Courot), and Paris (Etienne Jacotot). In Strasbourg, on the Esplanade campus, we are recruiting a research engineer/postdoctoral fellow (M/F) to start in early 2026 for a period of 24 months.

The candidate (M/F) will benefit from:

-Access to the laboratory by public transport (tram, bus)

-A staff restaurant on campus

-Transport: 75% of the cost covered and a mobility allowance of up to €300, subject to conditions

-Social benefits: contribution to health insurance, Social Action and Mutual Aid Committee (sports, leisure activities, tickets, etc.)

-44 days of leave + RTT/year

Contraintes et risques

Work with animals; daily monitoring. Submission of applications for authorization to work with animals (APAFiS) and human cells. No chemical or biological risks.