User:Dmierke

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Research in the Mierke group aims to develop therapeutic agents for the inhibition of different protein-protein interactions which have been verified as biomedical targets, including the proteins Rac1, cFLIP and NEMO which are important cancer targets. We are currently designing molecules that inhibit formation of the DISC (death Inducing signaling complex) important in the regulation of apoptosis, with emphasis placed on blocking the recruitment of cFLIP to the DISC, and thereby reinstating the extrinsic apoptosis signaling. Another project entails screening for direct inhibitors of the GTPase Rac1 oncogenic protein, employing a novel NMR-based GTP turnover assay. A final project aims at the identification of molecules to inhibit the NEMO/IKK association and thereby a novel method for therapeutic intervention. This multifaceted research includes multiple components: [1] molecular biology and biochemistry methods to express and purify proteins, and develop and run screening assays employing fluorescence anisotropy, ELISA, or fret based assays, [2] structure determination using x-ray crystallography complemented by high-resolution NMR methods which provide important insight for the rational design of inhibitors, [3] computational approaches (molecular modeling of proteins or protein complexes, docking of small molecule libraries, development of novel searching algorithms), and [4] the chemical synthesis of peptides and peptide libraries for screening.