The role of TBK1 and IKKε in aging and preventing systemic inflammation

• Applicant: Remzi Onur Eren, Ph.D.
• Subject Area: Immunology ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546095280

Cell death and the interferon response not only form the important basis of innate antiviral immunity but also play a role in inflammation, aging, and disease. Thus, delineating the regulation, as well as the physiological and pathological functions of molecules involved in the crosstalk between cell death and the interferon response, is important for understanding the pathogenesis of infectious, inflammatory, and aging-related diseases. TBK1 and its homolog IKKε induce antiviral interferon production downstream of nearly all nucleic acid-sensing molecules but also are involved in the negative regulation of the kinase activity of RIPK1, which has a well-described function in the induction of cell death. This places TBK1 and IKKε as a regulator of cell death and the interferon response. However, the role of TBK1 and IKKε in aging and tissue homeostasis, independently of their function in suppressing RIPK1-kinase activity-induced death, remains elusive. Here, we propose to study the mechanisms behind how TBK1 and IKKε regulates cell death and inflammation in health, disease, and aging, as well as the functional involvement of TBK1 and IKKε kinase activity in tissue homeostasis independently of their function in suppressing RIPK1-kinase activity-induced death. A better understanding of the importance of TBK1- and IKKε-mediated signaling in cell death and inflammation can lead to the development of future therapies for infectious, inflammatory, and aging-related diseases.

• DFG Programme: Research Grants