Projects Offered

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

Scientific Background

Circulating myeloid cells, which include monocytes, dendritic cells and granulocytes, are short lived and continuously replenished by the bone marrow. Under non-inflammatory conditions, myelopoiesis follows relatively ordered differentiation routes that sustain circulating monocytes and granulocytes and seed tissue macrophage and dendritic cell compartments. Both mature cells and bone marrow progenitors have the capacity to rapidly reconfigure during local and systemic inflammation, with cell–cell communication cues from stromal, endothelial, and lymphoid niches helping to calibrate output and function. 

Myeloid cell activation and exhaustion has both been described on a mature cell and progenitor cell level, leading to emergency myelopoiesis or hematopoietic halt/shock. Using single-cell and multi-omic profiling integrated with trajectory inference and ligand–receptor/network modeling, this project will establish a perturbation landscape of different myeloid cells and their progenitors in the context of different inflammatory cues using in silico modelling and in vitro validation.

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 cell biology at single-cell resolution. Combined with datamining, LLM studies, in vitro activation and CRISPR/Cas9 perturbation screen, you will study the activation and exhaustion landscape of different myeloid cell types and their progenitors. In addition, you will work together with the team to characterize inflammatory models in vivo that span both systemic and local inflammation and track myeloid cell and progenitor activation and exhaustion over time.

This PhD requires a strong background in immunology, previous experience with both wet lab and dry lab work on a single-cell level 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 (Activate) as your project 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 (2024) A time- and single-cell-resolved model of murine bone marrow hematopoiesis. Cell Stem Cell. Feb 1;31(2):244-259.e10. Link