Elucidating the role of genome instability in dendritic cells

• Applicants: Professorin Dr. Eva Kiermaier; Professorin Dr. Katrin Paeschke
• Subject Area: Cell Biology ; Immunology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504334432

The preservation of genome stability is one of the key tasks of all cells. DNA double strand breaks (DSBs) constitute deleterious DNA lesions, that can lead to mutations, deletions and consequently cell death. To ensure genome stability, mechanisms evolved to detect and correct DNA insults, which collectively are referred to as the DNA damage response (DDR). Yet, DNA DSBs can also occur during physiological processes such as meiosis or lymphocyte development pointing to a dual role of DNA DSBs in regulating cellular function and viability. Recent studies in macrophages indicate that DSB arise upon immune activation due to production of genotoxic agents (e.g., reactive oxygen and nitrogen species). These types of DSBs elicit a canonical DDR (cDDR) leading to activation of the cell cycle checkpoint (ATM) and DNA repair. In addition, those damage-associated proteins activate a non-canonical DDR (ncDDR), which is indispensable for cell differentiation, maturation, and immune activation. ncDDR represents a novel concept to harness DNA lesions as biochemical tool to regulate various cellular effector function. In this research proposal we aim to decipher the nature, causes and consequences of genomic DNA lesions in myeloid immune cells and gain novel insights into the physiological role of DNA aberrations during innate and adaptive immune responses.

• DFG Programme: Research Grants