DC 4 - Develop a technological platform to understand metabolism and cell-cell interactions in the immune system

• Objectives:

Aim of the project: We propose to employ this approach for the characterization of dendritic cell–T cell interactions—which are critical for T cell activation and fate determination—in the context of vaccination and in the tumor microenvironment. Data acquired in the context of this project will be instrumental in better defining transcriptional and metabolic pathways that influence these processes, with the potential to identify novel molecular targets that can be exploited for immune regulation.

1. integrate the existing LIPSTIC and uLIPSTIC technologies to track cell–cell interactions with tools that allow the assessment of the metabolic and transcriptomic state of cells at single-cell resolution;
2. validate and explore this novel approach by applying it to the characterization of dendritic cell and T cell interactions in response to vaccination;
3. understand the role of lipid metabolism in specific tissue microenvironments, including the tumor microenvironment.

• Brief project description:

Interactions between different cell types are key for immune function. To facilitate the study of the biological relevance of cell–cell interactions in the immune system, the PI developed novel technologies, called LIPSTIC and uLIPSTIC, which allow the identification and retrieval of cells participating in a given interaction in vivo for downstream analysis.

So far, the recording of interaction history with LIPSTIC has been successfully combined with single-cell RNA sequencing, thus allowing scientists to relate physical contacts between cells to the transcriptional states observed. By contrast, the fine-tuning of metabolic activity in immune cells, despite being a well-recognized layer of immune regulation, has not been explored in the context of immune interactions. Here, we propose to combine, for the first time, information on immune cell interactions with a deep characterization of cellular metabolic profiles, leveraging the different expertise present in the doctoral network. In detail, we propose to implement a pipeline that will merge LIPSTIC with immunometabolic profiling, SCENITH, and the CLICK-Uptake assay.

• Planned secondments:

Everts lab (Leiden University Medical Center, Netherlands)
• Get trained in immunometabolic profiling.

Finlay lab (Trinity College Dublin, Ireland)
• Get trained in CLICK-Uptake assays.

Argüello lab (Centre d’Immunologie de Marseille-Luminy, France)
• Get trained in SCENITH technology.