Transcriptional network heterogeneity of cellular senescence in single-cell resolution

• Applicant: Dr. Mathias Diehl
• Subject Area: Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 513057729

Aging is the primary risk factor for many human pathologies. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases, could have a tremendous impact on human health. Recent studies have demonstrated the importance of both genetic and environmental factors in modulating the aging rate. Particularly, when does aging begin and what is the dynamics of its progression are intriguing open questions. However, relatively little is known about vertebrates aging, due to the relatively long lifespans on classical models. To address this challenge, I will employ the naturally short-lived turquoise killifish as my primary genetic model. Focusing on senescent cells, my proposed research addresses these fundamental questions using multidisciplinary approaches, including single-cell and epigenetic profiling, genome engineering, and in-vivo imaging. Initially, I will use in-vitro models of senescence, in fish and mouse cells, to characterize the evolutionary-conserved senescence program, by identifying novel enhancers that are active during senescence. Next, I will generate fluorescent reporters for senescence in killifish, to explore how individual cells senesce in-vivo, by using innovative imaging techniques and advanced single-cell approaches. Ultimately, these experiments will reveal the spatiotemporal dynamics of senescence in-vivo, will allow to better design novel treatment strategies

• DFG Programme: WBP Fellowship
• International Connection: Israel
• Host: Dr. Itamar Harel