The focus of Dr. Peti’s research group is to understand the molecular mechanisms that regulates signalling enzymes. The group combines the information derived from biomolecular NMR spectroscopy, X-ray crystallography, and additional biophysical techniques, such as ITC, DSC, Biacore, and CD spectroscopy. Enzymes of key interests are ser/thr protein phosphatases (PP1, PP2B), tyr phosphatases and ser/thr kinases, especially MAP Kinases. Furthermore, my research group is pursuing an molecular understanding for the formation of bacterial biofilms.
Signaling cascades direct information and, in turn, function from memory to muscle movement important at any stage of life. These cascades are mediated by a network of highly specific, tightly regulated series of protein:protein interactions, including those made by Serine/Threonine kinases and Serine/Threonine phosphatases. The Peti group’s long-term goal is to achieve an in-depth understanding of this signaling network in the post synaptic density so we will be able to develop highly specific drugs for diseases such as Down's syndrome and mental retardation. Therefore the group has started to investigate the role of the Serine/Threonine phosphatase Protein Phosphatase 1 (PP1) in neuronal signaling, as it is one of the most important protein phosphatases in the brain. Two of the major interaction partners of PP1 in neurons are the large, multi-domain scaffolding proteins Spinophilin and Neurabin. These proteins target PP1 to its cellular point of action, the post synaptic density of dendritic spines. This targeting of PP1 by Spinophilin and Neurabin is responsible for the PP1-mediated regulation of glutamatergic AMPA/NMDA channel activity. To understand the Spinophilin/PP1 and Neurabin/PP1 signaling networks in molecular detail, we will use NMR spectroscopy to elucidate the scaffolding properties of the Spinophilin and Neurabin protein interaction domains, both as isolated domains and in complex with their interaction peptides and binding proteins. Spinophilin and Neurabin also bind and organize actin. It has been shown that this organization is of key importance for dendritic synapses shape and therefore for early childhood learning, development, and memory. Therefore, these 3-dimensional structures, interaction maps, and biochemical studies will provide a detailed understanding of this specificity and will allow us to selectively modulate particular signaling cascades for medical benefit.