Available Positions

Post-doctoral position for 2 to 4 years for an ANR-funded project

in Saint Antoine Research Center 

(INSERM, Sorbonne Université, Paris, France)

aiming at manipulating tryptophan metabolism in a therapeutic perspective in Inflammatory Bowel Diseases

Scientific goal

Chronic inflammatory diseases, including inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA) are immune-related disorders characterized by inappropriate inflammation. Their incidence has increased dramatically in Western countries in recent decades, supporting a role for environmental factors. Current therapies are only partially efficient and mostly based on immunosuppressants associated with side effects, including infection and neoplasia. New therapeutic strategies with innovative and more precise targets are thus urgently needed.

We identified an alteration of tryptophan metabolism in both IBD and RA and its role in pathogenesis. We notably pointed out the role of overproduction of pro-inflammatory metabolites at the expense of a decreased production of anti-inflammatory ones. By administrating a specific enzyme (that we produced and purified), which is downregulated in inflammatory contexts, we were able to counteract the tryptophan metabolism alterations and induce therapeutic effects in colitis and RA models ( https://gut.bmj.com/content/72/7/1296.long  and   https://ard.bmj.com/content/early/2023/12/01/ard-2023-224014.long )

The aims of the present project are to better understand the role of the gene encoding this enzyme in inflammatory contexts (particularly using recently generated conditional KO mice) and to characterize the effect of this therapeutic enzyme in pathological settings in order to develop it as a new therapeutic candidate. The Recruited postdoc will work on the intestinal inflammation aspect of the project. 

Partners involved  INSERM, Sorbonne Université, APHP, INRAE, Université de Lorraine.

The post-doctoral scientist will work in Harry Sokol’s Lab (https://www.crsa.fr/equipe-philippe-seksik.html) in Saint-Antoine Research Center in the heart of Paris and in collaboration with the ProbiHote Team in MICALIS Institute (Jouy-en-Josas, close of Paris) an Université de Lorraine. The position is vacant from March 2024 on a full-time basis and is integrated in an ambitious ANR-funded project.

Strategy

Wild type and KO (including mice generated for the project) mice will be used to evaluate the role of the gene of interest in intestinal inflammation. Several colitis models will be used as well as multi-omics analysis (bioinformaticians are present in the lab to analyze any type of omics). Experiments will also be done on primary human blood and intestinal cells. Results acquired in mice will be validated in human patient's samples using already constituted biobanks. The effect of the therapeutic enzyme will be characterized, and the mechanisms will be deciphered.

Required skills

We are looking for a highly motivated candidate who should have a recent PhD, be technically accomplished and have strong knowledge in immunology and/or metabolism. The candidate should have the required authorization to perform animal experiments. Some skills in intestinal inflammation would be a plus.

Besides the PI (Harry Sokol), the post-doctoral fellow will interact with senior scientists, other post docs, PhD students, engineers and technicians. He/she will also interact with other labs in France and abroad and with several platforms. The candidate will have to achieve the aims of the study and will have to regularly present the results to the partners involved.