IMIB - Institute for Molecular Infection Biology

Characterizing the temporal dynamics of host-pathogen interactions by combining single-cell nascent RNA-seq and genetic screen

Salmonella enterica is an intracellular pathogen displaying a complex interplay with the host immune system. As an example, Salmonella invasion usually triggers an initial inflammatory response leading to the polarization of the infected Macrophages toward a M1 "pro-inflammatory" state. Macrophages can remain pro-inflammatory and clear the infection or, conversely, their polarization state can be switched to a M2 "anti-inflammatory" phenotype. M2 Macrophages are more permissive to Salmonella development and numerous studies highlight the pathogen ability to actively induce the host cell reprogramming. However, to which extent the bacteria drives the Macrophage polarization and the exact mechanisms leading to these variations remain poorly understood.

Single-cell RNA sequencing (scRNA-seq) is a powerful technic to assess cell-to-cell variability based on transcriptomics. Notably, Erhard et al. introduced scSLAM-seq to investigate the early infection of Fibroblasts by the Cytomegalovirus. Over my research projects, I will adapt and apply scSLAM-seq to study the infection of Macrophages by Salmonella enterica serovar Typhimurium. I aim at recording the time-resolved transcriptional landscape of single Macrophages throughout the infection and understand why some Macrophages maintain a M1 polarization whereas others are sensitive to Salmonella-induced switching to the M2 state. Especially, I will focus on the identification and the characterization of key gene regulatory networks involved in these transitions.