Manipulating selected inflammatory responses in macrophages. (2018–2020)
This project aims to define the structural and functional interactions of a new transmembrane adaptor SCIMP. SCIMP has recently been shown to modulate Toll-like receptor signaling producing only selected pro-inflammatory cytokines. The atomic structure of the complex, phosphorylation, recruitment and function of SCIMP effectors and binding of a death regulator to SCIMP will be studied. The outcomes will include the first structure of this unconventional adaptor-receptor complex, SCIMP effectors for pathogen-specific responses and potential new cross talk between TLR4 driven inflammation and necroptosis. The benefits will include new knowledge about how specific cytokines are generated for tailored inflammatory responses in infection.