Vsevolod V (Seva) Gurevich
Vanderbilt University, USA
Title: Mass production of high fidelity oligonucleotides as feed stock of Post-genome-sequencing synthetic biology (PGS-SB)
Biography
Biography: Vsevolod V (Seva) Gurevich
Abstract
Virtually every protein is multi-functional. Over-expression or knockdown/knockout by definition enhance or suppress all functions of targeted proteins. Thus, these methods are inherently unsuitable to elucidate biological role of individual functions. Re-engineered of signaling proteins to enhance or suppress a single function out of many is a viable alternative. However, in contrast to over-expression or knockout, this approach requires in-depth knowledge of the molecular mechanisms of each function of the protein of interest. Relatively few proteins are studied in sufficient detail to make this possible. We will discuss this approach using arrestin proteins as an example. Arrestins are ultimate multifunctional scaffolds, organizing multi-protein signaling complexes and localizing them to particular subcellular compartments. Extensive mutagenesis and structural work revealed the molecular basis of at least some arrestin functions, enabling the construction of signaling-biased arrestins, as well as the use of their mono-functional elements to elucidate the biological role of their functions. Arrestins regulate G protein-coupled receptors, cell adhesion and motility, as well as MAP kinase signaling involved in life-or-death decisions of the cell. Therefore, reengineered “designer” arrestins and their parts are useful tools for experimental manipulation of cell behavior. Practically every disorder is associated with faulty signaling. Signaling-biased arrestins and other regulatory proteins allow us to channel cell signaling in desired direction, which has enormous therapeutic potential.