Computational Genomics of Signal Transduction

PROJECT SUMMARY Signal transduction is a universal biological process vital to all organisms. Due to their central role in disease, signal transduction systems in humans and in bacterial pathogens are the primary targets for drug design. Our long-term goal is to understand how cells detect, transmit, and adapt to signals. The main focus of our research is on bacterial signal transduction systems, with the goal of revealing their fundamental properties and mechanisms at the molecular level. The main unanswered questions that we propose to address are: (1) Which small molecule ligands are recognized by bacteria; (2) How did signaling networks evolve; and 3) Can we use the knowledge obtained with bacterial systems to advance our understanding of their counterparts in humans, especially with respect to disease. We propose to build on our previous findings and capitalize on our tools and innovative approaches to obtain and capture this knowledge as predictive models. These models will be stored in public databases, such as InterPro, NCBI Conserved Domain database, and our own Microbial Signal Transduction (MiST) database. Current MiST capabilities will be further enhanced to better serve the scientific community.