NJIT Associate Professor Edgardo Farinas has been awarded today a three-year $340,000 National Institutes of Health (NIH) grant to investigate spores as a protein display platform for the directed evolution of membrane proteins.“My long-term objective is to engineer proteins designed to order. My more specific aim is to stabilize G protein-coupled receptors which are membrane proteins and are involved in almost every physiological process,” said Farinas.
These proteins transmit most cellular responses across cell membranes through a vast array of extracellular stimuli, which include small molecules, light, proteins, peptides, hormones, and ions.
Irregular control of these proteins can lead to pathological conditions. As a result, they are major drug targets, and make up greater than 50 percent of the current human therapeutic market with annual revenue in excess of $50 billion.
Determining the three-dimensional structure is necessary to investigate the molecular details of activation/deactivation. However, there are few structures available because these proteins are difficult to crystallize. For instance, they suffer stability problems due to flexibility. Hence, a robust and efficient protein engineering system is needed to optimize these proteins for structural determination.
Farinas’ research will optimize these proteins using a random approach that mimics natural evolution in a test tube. The method is called directed or laboratory evolution. The unstable protein is the parent and a library of these protein offsprings will be created. The library will be screened for a desired fitness-stability, in this case. Once a winner is identified, it becomes the parent for another round of laboratory evolution. This is done in iterate cycles until the desired fitness is achieved.
In 2008, Farinas received a National Science Foundation (NSF) CAREER award for his project "New Tools for High-Throughput Screening of Protein Libraries: Engineering Metalloproteins Displayed on Bacillus Subtilis Spores." The prestigious career award recognizes teacher-scholars most likely to become the academic leaders of the 21st century. In 2010, he was awarded patent 7691616 B2 for his work entitled: “Cytochrome P450 Oxygenases.”
His most recent publications include “Directed evolution of CotA laccase for increased substrate specificity using Bacillus subtilis spores,” Protein, Engineering, Design and Selection (PEDS) (Elsevier 2010) http://peds.oxfordjournals.org/content/23/8/679.short and “Laboratory Evolution of Laccase for Substrate Specificity,” Journal of Molecular Catalysis B Enzymatic, Elsevier, 2010 http://www.sciencedirect.com/science/article/pii/S138111770900280X He holds a doctorate from the University of California, Santa Cruz and a bachelor’s degree from Loyola University of Chicago.