PhD fellowship in immunology and bioinformatics available (Team 1 – CRTI)
The team 1 at the Center for Research in Transplantation and Immunology (CRTI) in Nantes, France, is seeking for a highly motivated PhD student to work on the role of regulatory T cells during septic shock in human. This position is available for 3 year and is funded by ANR in the context of a collaborative project between Pr K Asehnoune (Coordinator) and Pr R Josien (WP leader). The candidate will work under the supervision of Pr R Josien and Dr. J Martin.
Student's training requirements
Highly motivated candidates holding a master’s degree with strong interests in the field of human immunology, single cell genomics and bioinformatics are welcome to apply. The candidate is expected to be able to work independently, while actively cooperating with other members of the group.
Between January and March 2021
- Motivation letter with research interests
- Contact information of at least two references
Online interviews of preselected candidates will be between January 4 and 15, 2021. To firstname.lastname@example.org before December 24th 2020
Sepsis causes more than 5 million deaths worldwide with an estimated cost of $ 17 billion annually in the USA. It is now assumed that most of the death is due to sepsis-induced immune suppression (SIIS) for which there is no FDA-approved specific therapeutic option. This SIIS renders septic patients prone to new secondary infections and alters their long-term functional status. The patients who die during the late phase of sepsis have usually an immune system that does not recover. However, the mechanisms of the SIIS are still poorly known. Severe alteration of the lymphocyte compartment is a hallmark signature of SIIS. A dramatic decrease of circulating CD4+ T cells and the persistence of an increased percentage of CD4+FoxP3+ regulatory T cells (Treg) cells were predictive of secondary nosocomial infections and poor outcomes in septic patients. There are good experimental evidences that Treg, which play a major role in immune suppression, impair the CD4+ T cell compartment during sepsis. We propose that one of the major mechanisms of SIIS is that TNF, released in high amount during sepsis, boosts expansion and suppressive activity of Tregs through the TNF receptor 2 (TNFR2) which is the working hypothesis of our research project.
To get further insight into the role of TNFR2+ and Treg in SIIS, our proposal will address the following specific aims: 1. To perform deep and unbiased profiling of TNFR2+/- Treg in patients during severe sepsis (D1 and D4) at the single cell level using Cellular Indexing of Transcriptome and Epitopes by Sequencing (CITE-seq) of blood CD4+ T cells. 2. To will study the role of TNFR2 and its downstream NF- kB signaling pathway expressed by Treg in SIIS by using conditional knockout mice that we have been recently developed, which are animal models not available by other groups. 3. To study the sensitivity to TNF of Treg from septic patients and the therapeutic effect of human TNFR2 antagonist on SIIS in humanized knock-in mice expressing the extracellular portion of human TNFR2 fused to the mouse intracellular TNFR2 tail.
The fellow will work on the aim 1 of this project and will develop the CITE-seq experimental approach (CITE-Seq) and bioinformatics to characterize in details Treg molecular remodeling and to identify gene programs associated with TNFR2+ in Treg during the course of sepsis in patients.
The successful candidate will join a dynamic and collaborative team with extensive exchange and benefit from excellent scientific environment within the CRTI and the biomedical research campus, state of art research facilities and access to human samples. The CRTI is a multidisciplinary research unit located at Nantes University Hospital in the center of the city and is affiliated to INSERM and Nantes University. The CRTI develops disease-oriented basic and translational research and training programs aiming primarily at: 1. Understanding the mechanisms by which the immune system promotes or control diseases or lesions in transplantation, autoimmune, inflammatory and infectious disease; 2. Translating these advances from the laboratory to the clinic by bringing new diagnostic and immunotherapeutic developments; 3.Developing alternative strategies for organ or tissue replacement or repair.