※本セミナーは英語で実施されます。Seminar Language: English
【会場】山手3号館2F 西 大会議室
Dr. Christian GRIESINGER
Professor, Max Planck Institute for Multidisciplinary Sciences
Small molecules triggering transmembrane signaling and interfering with aggregation important in neurodegeneration
The effect of small molecules on proteins will be in the center of the lecture regulating bacterial signal transduction and interfering with aggregation of proteins involved in various cellular processes including neurodegenerative diseases. For both projects, Nuclear Magnetic Resonance (NMR) spectroscopy plays a crucial role.
Bacterial signal transduction relies for thousands of metabolites and other environmental signals on two component systems consisting of a kinase receiving the signal and a regulator that initiates expression of proteins responding to the signal. The signal is received on the extracytosolic side and needs to be transmitted through the membrane to the cytosolic kinase. A signal transduction mechanism will be presented for the citrate sensor CitA which is the first for this calls of molecules and might be abundantly used for thousands of two component system kinases.
Protein aggregation occurs in many biological processes including neuro- and cellular degeneration. In the lecture, the activity of a small molecule, anle138b, interfering with aggregation of prion protein (Creutzfeld Jakob disease), a-Synuclein (Parkinson’s disease and Multiple System Atrophy), Amyloid-b and tau (Alzheimer’s disease) as well as human islet amyloid polypeptide (type II diabetes mellitus) in mouse models of the disease will be discussed. Structures of the end point of aggregation in the presence and absence of anle138b will be shown for a-Synuclein and Amyloid-b revealing commonalities in the binding or anle138b. In addition, a structure of a toxic a-Synuclein oligomer will be presented. Further fields of biology in which aggregation and its inhibition play a role will be discussed.