TIRI · Role of the kinase TAOK2 in the innate immune response to viral infection
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-09-01 → 2025-08-31
- EU contribution
- €189,687
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Role of the kinase TAOK2 in the innate immune response to viral infection
Viral infections constitute a major threat to public health with a significant impact on life expectancy, quality of life, and the economy. One of the first warning signs of viral infections is the presence of viral nucleic acids within the cell. Pattern recognition receptors (PRR), specialized molecules that bind to invading viral RNA, trigger the innate immune response, culminating in the production of cytokines and chemokines and the expression of protective antiviral proteins. A dysbalanced innate immune response renders patients highly susceptible to virus infections or, conversely, leads to overactive immunity associated with autoimmune disease. We previously identified the protein kinase TAOK2 as a new player in the detection of viral RNA. In the absence of TAOK2, cells are less able to fight viral infection, and the induction of the innate immune response is compromised. In this project, I will define how TAOK2 recognizes viral RNA and how that affects the processes leading to the induction of the innate immune response. This will shed light on how the innate immune response, which needs to be kept in a delicate balance to fight off viral infection without overreacting to benign signals, is modulated and fine-tuned.
Data: CORDIS, © European Union
Project objective
Viral infections are a major threat to public health worldwide. The innate immune response acts as the first line of defense during viral infections by recognizing pathogen-associated molecular patterns such as double-stranded RNA (dsRNA). Impaired innate immune signaling sensitizes patients to viral infections, while aberrant innate immune activation is associated with autoimmune diseases. Recently, the host laboratory identified the protein kinase TAOK2 as a novel co-factor for viral dsRNA sensing. TAOK2 binds and is activated by dsRNA, and its depletion leads to an impaired immune response to viral infection. Notably, a mutation in TAOK2 causes immunodeficiency in human patients. These findings suggest a previously unappreciated role for TAOK2 in innate immunity, but the molecular details remain unclear.I will use synergistic biochemical, systems biology and in vivo approaches to comprehensively define the role of TAOK2 in innate immunity. First, I will use state-of-the-art biochemical and structural approaches to define the mechanism of dsRNA recognition by TAOK2 and discern the molecular basis for the disease-causing point mutation. Second, I will perform a multi-level systems biology analysis to integrate TAOK2 into a dynamic signaling network in response to viral infection. Third, I will assess the consequences of complete loss of TAOK2 and the clinically relevant TAOK2 point mutation in vivo using mouse models. This highly interdisciplinary and collaborative project will combine my existing expertise in biochemistry and in vivo approaches with the systems biology competencies of the host laboratory. Thereby, I will gain novel insight into the signaling network that governs the innate immune responses to viral dsRNA. The training during this project will increase my scientific and transferable skills, reintegrate me into the European research community, and thereby help me achieve professional maturity and academic independence.
Original text from CORDIS.
Participants
- TECHNISCHE UNIVERSITAET MUENCHEN · MuenchenCoordinatorGermany
Links
- View on CORDIS
- DOI: 10.3030/101064916
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e507419e7b&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5218e50dc&appId=PPGMS
Data: CORDIS, © European Union