Projects Offered

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

Scientific Background

Circulating myeloid cells, which include monocytes, dendritic cells and granulocytes, are continuously replenished to maintain tissue homeostasis at steady state and have the capacity to rapidly reconfigure during local and systemic inflammation. Under non-inflammatory conditions, myelopoiesis follows relatively ordered differentiation routes that sustain circulating monocytes and granulocytes and seed tissue macrophage and dendritic cell compartments, with cell–cell communication cues from stromal, endothelial, and lymphoid niches helping to calibrate output and function. In contrast, inflammatory perturbations can shift both the composition and behavior of myeloid populations through altered cytokine landscapes, trafficking programs, and tissue-derived signals. 

This reprogramming however does not only happen at the site of inflammation but also alters the bone marrow niche, affecting myelopoiesis, differentiation and stromal interaction, leading to emergency myelopoiesis or hematopoietic halt/shock. Using single-cell and multi-omic profiling integrated with trajectory inference and ligand–receptor/network modeling, the project will map how inflammatory signals reroute progenitor-to-effector differentiation, expand specific myeloid subsets, and reshape functional programs. It will test the concept that inflammation induces not only accelerated “emergency” output but can also produce phases of progenitor dysfunction or suppression—where stem/progenitor compartments enter protective quiescence, exhaustion, or shock-like states—resulting in delayed or maladaptive reconstitution. 

PhD Project: Defining Myeloid cell Ageing and its immunological impact on a single cell level

In our lab, we have established an integrated toolkit to study myeloid biology at single-cell resolution, combining single-cell sequencing with large, high-dimensional flow cytometry panels and a suite of transgenic mouse lines. In addition we utilize well-characterized inflammatory models that span both systemic and local inflammation, enabling us to track myeloid populations across compartments and over time with high phenotypic and molecular precision.

Building on these resources, this project aims to profile myeloid cell dynamics, poiesis, and the myeloid interactome in bone marrow and peripheral tissues at steady state and under local versus systemic inflammation to define changes in myeloid cell output and reprogramming leading to functional consequences for comorbidities and ageing-related immune dysfunction.

This PhD requires a strong background in immunology, previous experience with complex phenotyping of immune cells via single-cell sequencing including sequencing library preparation, bioinformatics and a willingness to work with in vivo animal models, including handling, experimental design and tissue processing and analysis.

If you are interested in this project, please select Mayer (Dynamics) 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

Bosteels C, Neyt K, Vanheerswynghels M, van Helden MJ, Sichien D, Debeuf N, De Prijck S, Bosteels V, Vandamme N, Martens L, Saeys Y, Louagie E, Lesage M, Williams DL, Tang SC, Mayer JU, Ronchese F, Scott CL, Hammad H, Guilliams M, Lambrecht BN. (2020) Inflammatory Type 2 CDCs Acquire Features of CDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection. Immunity, 52 (6), 1039-1056 e9. Link

Kucinski I, Campos J, Barile M, Severi F, Bohin N, Moreira PN, Allen L, Lawson H, Haltalli MLR, Kinston SJ, O'Carroll D, Kranc KR, Göttgens B. A time- and single-cell-resolved model of murine bone marrow hematopoiesis. Cell Stem Cell. 2024 Feb 1;31(2):244-259.e10. Link