Investigate how molecular networks of CD4 T cells shift during the critical transition from acute to chronic neuroimmune stresses

Christophe Chapelle, PhD supervisor: Feng He

This project will experimentally study if and how CTs occur in the immune system and if early warning signatures can be used for potential therapeutic interventions. FH’s group is interested in exploring gene expression dynamics and the underlying regulatory networks (He 2009; He 2014), currently focusing on T-cells by measuring and analysing genome-scale time-series data (He 2012; He 2013). The experimental data will be further analysed by the theoretical partners of the DTU. The project will study a well-known phenotype that the human immune system might be impaired after a long-term exposure to chronic stresses. This observation has been reported for a long time (Dhabhar, 2008) but the detailed corresponding molecular mechanism remains elusive. This project aims to understand how human CD4 T-cells evolve to shift the response efficiencies over time under the exposure of a chronic psychological stressor (e.g., sympathetic nervous system-mediated adrenergic stress) in an in vitro experimental model. Through the analysis of time-series transcriptome and high-throughput cellular marker detection by high-end cytometry (e.g., CyTOF), we will have an opportunity to illustrate when and how the CD4 T-cells show early warning signals by developing and applying advanced CT theories. The success of the study will identify potential drug targets to prevent a potential immune crash.

FH’s group will train the PhD candidates of the DTU on the following aspects: 1) experimental molecular immunology; 2) theoretical molecular and cellular immunology; 3) biostatistics; and 4) network-guided key gene discovery. FH’s group will bridge two local Luxembourg biomedical institutes: the LIH and LCSB. Through FH’s group, the PhD candidates within the DTU can access the experimental platforms and core facilities of both institutes, allowing the candidates to expand the know-how on new experimental techniques and also to utilise advanced immunological devices. In particular, the single-cell platforms established at LCSB (AS’s group) will allow for a new depth in analysis that, together with the novel analysis approaches developed by the theoretical groups, will lead to new insights into the role of chronic stress in immune responses.

The large-scale time-series experimental data generated by FH’s group will be further analysed and modelled by theoretical groups. The computational analysis results will in turn give feedback to FH, who will further validate the computational predictions in immunology and provide a basis to improve the corresponding computational models and approaches.