Mots-Clés

single cell OMICS T cell TCR signaling immuno-oncology

Description

Internship project:

 T cell receptor (TCR) signaling plays a crucial role in the maturation and differentiation of thymocytes. Disruptions in this signaling pathway can lead to dysregulations in thymopoiesis, with potentially pathological consequences. This internship will focus on studying the effects of TCR signaling disruption in murine models using single-cell RNA sequencing (scRNAseq) approaches. We use models in which certain components of the TCR signaling pathway are mutated, disrupting the normal development of thymocytes. The aim of this internship will be to analyze scRNAseq data from these models to study alterations in thymopoiesis.

The bioinformatics analysis of the data will focus on the following steps:

1. Preprocessing and quality control of the different datasets;
2. Merging or integrating datasets after evaluating the potential presence of batch effects;
3. Identifying markers of physiological thymopoiesis stages;
4. Comparing pathological thymocytes with classical thymopoiesis to identify dysregulations related to TCR signaling.
5. Ultimately, we aim to better understand how TCR signaling disruption influences thymocyte fate and to characterize the transcriptional regulatory networks underlying these processes.

If the student wishes, to have a better knowledge of the experimental work, he/she may also participate in generating a scRNAseq dataset although it will not be possible to use it for analysis during the short period of a M2 internship.

disciplines involves

The internship combines expertise from:

• Immunology: Focusing on T cell biology and the molecular mechanisms governing thymocyte differentiation and its perturbation leading to pathologies such as cancer.
• Bioinformatics: Involves the processing and analysis of large-scale scRNAseq datasets, requiring skills in data analysis and computational biology.
• Molecular Biology: Understanding the genetic and signaling pathways involved in TCR-mediated thymocyte development.

Future opportunities: If the internship progresses well and the student wishes to pursue a PhD, we are highly motivated to support an application to "La Ligue contre le Cancer" and to help prepare for doctoral school competitions.