Single-cell ribosome profiling to monitor the translational landscape in skin wound healing
Grantee: Ataman Sendoel, Assistant Professor, University of Zurich
Amount: DKK 3,979,800
Grant category: Research Grants in open competition
Year: 2024
Geography: Switzerland
Ataman Sendoel’s project seeks to improve our understanding of how genes are translated to protein during wound healing and clarify the potential of the involved pathways as drug targets.
Impaired wound healing poses a substantial medical challenge, particularly among the elderly. Understanding the gene expression changes during wound repair is therefore essential for devising new strategies to enhance wound healing in aging and disease.
While transcriptional (i.e., going from DNA to messenger-RNA) control has been extensively studied in the skin, recent studies have indicated that cellular behavior is strongly coupled to the regulation of translation (i.e., going from messenger-RNA to protein). However, how translation is controlled during wound repair and how its deregulation mechanistically contributes to impaired wound repair in aging remains unknown.
In this project, Ataman Sendoel and his team will exploit an in vivo strategy to comprehensively map the function of the translational landscape in skin wound healing. Leveraging a single-cell ribosome (an intracellular protein complex that translates messenger-RNA to protein) profiling strategy in vivo, the team will monitor skin cells during different wound healing stages. By coupling this with single-cell RNA sequencing, they will determine cell-type-specific translational efficiencies and identify factors relevant to wound repair in aging.
Finally, Ataman Sendoel and his team aim to carry out a mini-screen to identify FDA-approved drugs that selectively increase the translational efficiency of skin wound repair factors.
Collectively, these data will provide systematic insights into the translational landscape of skin wound repair, and how deregulated translation leads to impaired wound repair. It may also clarify if protein synthesis pathways could be targeted therapeutically to restore wound healing.