DFG Collaborative Research Centre 1444

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.