Research will be conducted at the Ecole normale supérieure (part of PSL University), the leading academic and research institution in France. It is located in the heart of the Latin quarter, among a high density of top research institutions. Your appointment will be with the Centre national de la recherche scientifique, which coordinates public research in France.
Motivation: Vertebrates use a diverse repertoire of adaptive immune receptors, such as T-cell receptors (TCR) to protect themselves against pathogens and internal aberrations such as malignant cells. Recent progress in high-throughput sequencing now allows for the deep profiling of individual repertoires. This repertoire sequencing (RepSeq) holds great promise for determining the immune status of individuals, measuring their response to vaccines or immunotherapies, and predicting their response to infections. However, if we want to use immune repertoires as a diagnostic tool in medicine or induce modifications in repertoires to target disease, we need to have a very good idea of what constitutes the repertoire of a healthy individual and how it develops.
Goal: The goal of this PhD project is to develop statistical mechanics-inspired tools of data analysis to understand how positive and negative selection during thymic development shape the healthy T cell repertoire, and impact T cell phenotype and function.
Approach: We will obtain RepSeq data of well-defined T cell sub-populations from our collaborators at the Weizmann Insitute. These sequences will be sampled during their development in the thymus. The project aims to develop novel analysis tools inspired by statistical mehchanics of disordered systems and tailored experiments to identify signatures of (positive and negative) selection during thymic development. This will promote our understanding of how thymic selection shapes the healthy TCR repertoire, and drive investigation of potential links between thymic selection and pathologies such as autoimmunity.
Elhanati, Y., Murugan, A., Callan, C. G., Mora, T., & Walczak, A. M. (2014). Quantifying selection in immune receptor repertoires. Proceedings of the National Academy of Sciences, 111(27), 9875–9880. http://doi.org/10.1073/pnas.1409572111
Sethna, Z., Elhanati, Y., Dudgeon, C. S., Callan, C. G., Levine, A. J., Mora, T., & Walczak, A. M. (2017). Insights into immune system development and function from mouse T-cell repertoires. Proceedings of the National Academy of Sciences, 114(9), 2253–2258. http://doi.org/10.1073/pnas.1700241114
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