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DFG Collaborative Research Centre 1444

This Collaborative Research Centre aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.

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Subproject 2 - Principal Investgators

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

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.

Founded by the DFG (Project Number: 427826188)