Assessment Report of the CNRS (Centre National de la Recherche Scientifique)

The Centre national de la recherche scientifique (CNRS) is a public scientific and technological institution under the supervision of the minister in charge of research. Its main missions, defined by decree, are i) to carry out, alone or with its partners, all research of interest to the advancement of science and the economic, social, and cultural progress of the nation; ii) to contribute to the application and use of the results of this research; iii) to develop scientific information and access to research work and data, by promoting the use of the French language; (iv) to contribute to training in and through research. The CNRS covers all fields of science. It is organized into ten scientific Institutes. It had a total budget of €3.7 billion in 2021, €2.8 billion (76%) of which came from public subsidies allocated by the French national government, and €0.9 billion (24%) of which came from own-source revenue. The staff represented 31,876 FTE (full-time equivalent), including 23,873 FTE permanent staff and 8,003 non-permanent staff. The CNRS research activities are organized into more than 1,000 research units (or laboratories), which are almost always shared with other institutions, mainly universities or other national research organizations and “grandes écoles”. They are called “joint research units” (in French “unités mixtes de recherche” or “UMRs”). There are 109,800 persons in CNRS UMRs, i.e. over 40% of the total workforce of the French public research ecosystem; 27% of them are CNRS employees. The CNRS UMRs are spread among more than 80 cities in France. The international assessment committee was tasked by the High Council for evaluation of research and higher education (Hcéres) with conducting an external assessment of the CNRS for the 2017-2021 period. The committee consisted of scientists and leaders from the worlds of universities, research organizations, technology transfer organizations, and business and industry. The review was concerned with the CNRS in its entirety as well as its interplay with the French research and higher education eco system, but not with a detailed review of the constituent Institutes or of particular scientific disciplines. The assessment process entailed a review of a self-assessment report that was prepared by CNRS leadership, and a succession of committee meetings prior to a week-long in-person review that occurred May 8-12, 2023. The agenda for the in-person visit included extensive discussions with CNRS leadership, including for each of the 10 constituent Institutes, visits to university sites and UMRs, on-site meetings with junior and senior scientists and support staff, and meetings with CNRS partners universities, corporations and French and European national research organizations. More details on the agenda of the visit are provided at the end of the report. The committee is very grateful for the support it received from Hcéres and the CNRS teams throughout the review

Pivotal role of intestinal cholesterol and nuclear receptor LXR in metabolic liver steatohepatitis and hepatocarcinoma

: Hepatocellular carcinoma (HCC) incidence is continuously increasing worldwide, due to the rise of metabolic dysfunction-associated steatohepatitis (MASH) cases. Cholesterol is an essential driver of the metabolic dysregulations that promote HCC progression. Liver X Receptor (LXR) is a nuclear receptor best known for the regulation of lipid and cholesterol homeostasis, with a prominent function in the liver and in the intestine. Here, we aimed to explore whether modifications in intestinal lipid metabolism may contribute to the onset of HCC, particularly taking into account cholesterol metabolism and LXRs. To study the progression of MASH to HCC, we induced metabolic HCC in wild-type male mice and mice carrying an intestinal chronic activation of LXRα. Also, we analysed human hepatic transcriptome datasets. The increased consumption of fat and carbohydrates drives the intestinal activation of LXRα and accelerates the onset of the hepatic tumours. Chronic intestinal-specific activation of LXRα enhances HCC progression only in the presence of a high cholesterol intake. In HCC, despite the increased hepatic cholesterol content, LXR is not active, thus driving liver cancer development. Intriguingly, in line with these results in the mouse model, LXR transcriptome is also downregulated in human hepatocarcinoma and its expression level in liver tumours directly correlates with a decreased survival rate in patients. Overall, our findings establish the relevance of the intestine in influencing the susceptibility to MASH-HCC and point to intestinal LXRα activation as a driver of metabolic liver cancer in the presence of dietary cholesterol