Projects Offered

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

Scientific Background

Myeloid cells, which include monocytes, macrophages, dendritic cells, and granulocytes, sit at the frontline of immune defense and tissue homeostasis, yet they are also among the immune compartments most visibly remodeled by ageing. These changes are influenced by several hallmarks of ageing and a central aim will be to disentangle intrinsic (cell-autonomous) from extrinsic (environment-driven) hallmarks of ageing and determine how they reshapes myeloid biology. Intrinsically, accumulated DNA damage, epigenetic drift, telomere attrition, mitochondrial dysfunction, impaired proteostasis/autophagy, and heightened cellular senescence programs can bias myeloid differentiation and survival, rewire metabolic set-points, and “pre-tune” signaling thresholds, leading to exaggerated inflammatory outputs or blunted immunological functions. Extrinsically, the ageing tissue environment shows chronic low-grade inflammation, altered cytokine and growth-factor availability, changes in stromal and endothelial cues, shifts in the microbiome and barrier integrity, and increased exposure to senescence-associated secretory phenotypes (SASP) can continuously imprint new activation states on myeloid cells, driving maladaptive inflammation, defective tissue-repair polarization, and compromised antigen presentation.

Together, these intrinsic and extrinsic changes coincide with age-associated shifts in hematopoiesis and a rising inflammatory baseline (“inflammageing”), yielding myeloid populations with altered pattern-recognition signaling, cytokine production, metabolic profiling and migratory behavior. These changes are highly relevant and linked to poorer vaccine responses, increased infection risk, chronic inflammatory pathology, and impaired tissue repair, yet the field still lacks a precise, cell-type–resolved definition of “myeloid ageing”.

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

In our lab we have developed a number of tools to study myeloid cells on a single cell level. This includes single-cell RNAseq and large high-dimensional flow cytometry panels and a collection of transgenic mouse models specifically engineered for the reporting, lineage tracing, or conditional deletion of defined dendritic cell subsets. In this project the aim is to profile the tissue-specific myeloid cell single-cell landscape of young and old mice, establish tissue-specific murine models of premature ageing, define myeloid population specific SASP and mitochondrial signatures and thus unravel cell-intrinsic and extrinsic hallmarks of myeloid cell ageing.

This PhD requires a strong background in immunology, previous experience with the complex phenotyping of immune cells on a single-cell level and proficiency in working with in vivo animal models, including handling, experimental design and tissue processing and analysis. Experience in bioinformatics is a plus.

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

Chen B & Mayer JU. (2026) Emerging Frontiers in the Mitochondrial Regulation of Dendritic Cell Biology. Redox Biol, 104032. 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

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. (2023) Hallmarks of aging: An expanding universe.Cell. Jan 19;186(2):243-278. Link