Events

CBE/ENGR 225 Faculty Seminar Series Presents: Eric J. Deeds, Ph.D. Associate Professor Department of Molecular Biosciences The University of Kansas, Tues., April 17, 2018

Tuesday, April 17, 2018, ESB #2001

Eric J. Deeds, Ph.D.

Associate Professor
Department of Molecular Biosciences
The University of Kansas 
Tuesday, April 17, 2018
ESB #2001
4pm-5pm
*Light refreshments will be provided*

Host: Linda Petzold
The Evolution of Crosstalk in Signaling Networks

ABSTRACT: The degree of crosstalk observed in signaling networks varies widely across organisms. In metazoans, crosstalk is widespread, with some kinases and phosphatases acting on hundreds of downstream targets. In bacteria, however, signaling pathways are often completely isolated from one another.  It is currently unclear exactly what pressures have driven the evolution of these vastly different topologies.  The basic "building block" of metazoan signaling networks is a pair of enzymes, one that modifies a substrate (e.g. a kinase) and one that undoes this modification (e.g. a phosphatase).  We have used mathematical models to show that adding crosstalk to this type of system can increase ultrasensitivity and couple signal responses, behaviors that could yield phenotypic benefits for metazoan cells.  In contrast, bacterial networks utilize Two-Component Signaling (TCS), in which a single enzyme (the sensor Histidine Kinase, or HK) acts as both kinase and phosphatase for its downstream Response Regulator (RR).  We found that crosstalk always reduces signal response in TCS, which likely underlies the dramatic decrease in fitness that has been observed experimentally when crosstalk is engineered into bacterial cells.  Our work thus indicates that the different topologies of metazoan and bacterial signaling networks may arise, at least in part, from fundamental differences in the biochemistry of the basic motifs from which the networks themselves are constructed.  More recently, we have found that high levels of crosstalk in metazoans has likely evolved to allow different cell types to respond in different ways to the same environment.  In addition to providing an evolutionary rationale for the incredible complexity of metazoan signaling networks, our findings have implications for efforts to rationally target such networks in the treatment of cancer and other diseases.