Felix Meissner Laboratory

Target and Pathway Deconvolution

Which cellular targets and pathways are engaged by immune activators and inhibitors?

Project details

Ligand-receptor and small molecule-protein interactions trigger cell type- and context-specific immune functions. The molecular mechanisms how immune activation and inhibition is sensed by receptors of endogenous and pattern recognition receptor-ligands and processed intracellularly is, however, often unknown. A prominent example is the still enigmatic activation of the NLRP3 inflammasome.

Intracellular signaling cascades are tightly regulated by rearrangements of protein networks governed by covalent and often reversible post-translational protein modifications (PTMs), as well as by interactions and translocations of distinct sets of proteins. Experimental approaches that quantitatively capture dynamic signaling networks are therefore valuable for establishing causal links to cellular phenotypes and developing strategies for targeted interference.

We employ a combination of proteomics methods to dissect intracellular immune signaling mechanisms. Focussing on PTMs, we have revealed novel intracellular immune signaling checkpoints such as the dephosphorylation of NLRP3 together with Eicke’s lab (Stutz et al 2017) and the ISG15ylation of TRAF2 (Frauenstein et al 2021). We further use proteomics target deconvolution, including thermal proteome profiling as powerful methods to identify direct targets of immune activators and inhibitors, and biochemical fractionation to unbiasedly map intracellular protein network rearrangements (Meissner et al 2022 in press).

Project-related publications

The Emerging Role of Mass Spectrometry-based Proteomics in Drug Discovery

Meissner F, Geddes-McAlister J, Mann M, Bantscheff M

Nature Reviews Drug Discovery in press

Identification of covalent modifications regulating immune signaling complex composition and phenotype

Frauenstein A, Ebner S, Hansen FM, Sinha A, Phulphagar K, Swatek K, Hornburg D, Mann M, Meissner F

Mol Syst Biol. 2021 Jul;17(7):e10125

Project-related funding

SFB 914

Deutsche Forschungsgemeinschaft (DFG)

GIF

German-Israeli Foundation

Project-related scientists

Felix Meissner Lab
Felix Meissner Lab
Felix Meissner Lab
Felix Meissner Lab

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