Projects Offered

1 PhD project offered in the IPP winter call Molecular Biomedicine & Ageing

Scientific Background

Type 2 immunity is a specialized branch of the immune response primarily orchestrated to combat extracellular particles, by removing or encapsulating them. Main orchestrators are T helper 2 (Th2) and innate Lymphoid cells, which secreting cytokines including IL-4, IL-5, IL-9, and IL-13. These cytokines promote the recruitment and/or activation of eosinophils, basophils, mast cells, and alternatively activated macrophages. While essential for host defense against parasitic infections, dysregulated type 2 immune responses also contribute to the pathogenesis of allergic diseases such as asthma and atopic dermatitis.

Damages of the epithelium, alarmin responses and Dendritic cell activation have all been implicated in the induction of type 2 immunity and potential differences between helminth induced and allergy associated type 2 immunity. However, the detailed interactions between involved vs bystander cells and the resulting activation and induction of type 2 immune responses are incompletely understood. Thus, treatment approaches to stop the development of type 2 immunity are lacking, as are pathways that specifically regulate the development of allergies, while retaining anti-parasite and wound healing responses. 

PhD Project: Mapping the immune cell interactome in type 2 immunity

In this PhD project we aim to study the immune cell interactome in type 2 immunity. Our previous work has identified unique dendritic cell populations that seem specialized to induce type 2 immunity towards parasite products. If these dendritic cells also mediate type 2 immunity against other antigens, such as allergens or environmental triggers, and if those responses result in a uniform or distinct quality of Th2 cell are important questions to be addressed. 

Our previous work could also show that interactions between antigen-presenting and bystander dendritic cells can be associated with distinct gene expression patterns and immunological outcomes. However, current interactome analyses have so far been limited to inferred interactions based on cellular receptor-ligand expression patterns. New technological advances now allow us to study physically interacting cells to define a temporal interactome. 

In this PhD project, developing these tools in in vitro explants, in vivo models and patient samples of type 2 immune disease will be critical to map and characterize key events that lead to different qualities of type 2 immunity and experimentally validate these interactions as potential therapeutic targets. Critical interactions and signaling pathways will then be extrapolated to existing single-cell RNAseq libraries of type 2 immune patients.

This PhD requires a strong background in immunology, previous experience with complex phenotyping of immune cells and wet-lab, as well as dry-lab skills.

If you are interested in this project, please select Mayer (Interactome) as your group preference in the IPP application platform.

Publications relevant to this project

Mayer JU, Hilligan KL, Chandler JS, Eccles DA, Old SI, Domingues RG, Yang J, Webb GR, Munoz-Erazo L, Hyde EJ, Wakelin KA, Tang SC, Chappell SC, von Daake S, Brombacher F, Mackay CR, Sher A, Tussiwand R, Connor LM, Ortega DG, Jankovic D, Gros GL, Hepworth MR, Lamiable O, Ronchese F. (2021) Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization. Nat. Immunol.,1 (13). Link

Giladi A, Cohen M, Medaglia C, Baran Y, Li B, Zada M, Bost P, Blecher-Gonen R, Salame TM, Mayer JU, David E, Ronchese F, Tanay A, Amit I. (2020) Dissecting Cellular Crosstalk by Sequencing Physically Interacting Cells. Nat. Biotechnol., 38 (5), 629–637. Link

Vonficht D, Jopp-Saile L, Yousefian S, Flore V, Simó Vesperinas I, Teuber R, Avanesyan B, Luo Y, Röthemeier C, Grünschläger F, Fernandez-Vaquero M, Fregona V, Ordoñez-Rueda D, Schmalbrock LK, Deininger L, Yamachui Sitcheu AJ, Gu Z, Funk MC, Mikut R, Heikenwälder M, Eggert A, von Stackelberg A, Kobold S, Krönke J, Keller U, Trumpp A, Hegazy AN, Eckert C, Hübschmann D, Haas S. Ultra-high-scale cytometry-based cellular interaction mapping. Nat Methods. 2025 Aug 7.Link