Impact of epigenetic regulation on T subsets involved in bone fracture healing (P02)

• Subject Area: Medical Informatics and Medical Bioinformatics
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427826188

Polansky-Biskup and Volk will investigate which impact epigenetic regulation of T subsets has on bone fracture healing. They want to identify the critical epigenetic players ('epigenetic switch regions') driving the differentiation, migration and function of the harmful pro-inflammatory effector T cells (Teff) and the beneficial regulatory T cells (Treg) during successful or impaired bone regeneration. For this, Polansky-Biskup and Volk will generate detailed molecular signatures (epigenome, transcriptome, surface proteome, T cell receptor profile) of primary human Teff and Treg cells from ex vivo material from bone fracture patients. Then, they will use state-of-the-art CRISPR-dCas9-mediated epigenetic editing to 'switch' the identified epigenetic regions and with that, to reprogram the functional T cell phenotypes. The generate 'epi-edited' T cells will then be tested in in vitro human osteogenesis and bone homeostasis models for their possible functional contribution to successful or impaired bone regeneration.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1444: Directed Cellular Self-Organisation for Advancing Bone Regeneration
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professorin Dr. Julia Polansky-Biskup; Professor Dr. Hans-Dieter Volk