Professor Gianluigi Veglia

Project Title: 
Biomolecular Simulations of Soluble and Membrane-Bound Complexes

This research focuses on the investigation of the molecular mechanisms that regulate cell signaling in multicellular organisms. Signal specificity is encoded into the 3D structure of proteins that transfer specific information from the cell surface to the nucleus, leading to changes in gene expression and cellular biochemistry. This lab studies these signaling processes examining how aberrant protein interactions and structural variation may lead to pathophysiologies of calcium signaling in cardiac and skeletal muscle. Calcium is a central messenger for contractility, and dysfunctional calcium signal transduction is linked to several pathologies including heart failure and muscular dystrophy. There has been a continuous effort to develop small molecules and protein therapies to ameliorate these pathological conditions. To elucidate the biochemical and structural bases for these processes, these researchers determine the 3D structures of protein complexes that are involved in calcium trafficking. Toward this end, the group is developing new structural biology approaches using Nuclear Magnetic Resonance (NMR) spectroscopy to obtain structural information on these large macromolecular complexes. They also study two important post-translational modifications central to calcium signal transduction and protein recognition: phosphorylation and myristoylation. Computational approaches are fundamental to understanding and interpreting the conformational dynamics information obtained from NMR studies. Toward this goal, the researchers have established a strong collaboration with the group of Jiali Gao (Chemistry). The overall goal of this research is to decipher the mechanisms underlying cell signaling and develop new frameworks for innovative therapeutic approaches.

Project Investigators

Cristina Olivieri
Todd Rappe
Professor Gianluigi Veglia
Dr Manu Veliparambil Subrahmanian
 
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