STKE Focus Issue on Systems Biology: Painting the Signaling Picture

A wealth of molecular, cellular, and biochemical information on a vast array of cellular processes is now complemented by a treasure trove of genomic and proteomic information. Can whole pictures of biological functions now emerge from these disparate parts? The special issue of Science magazine focuses on the interdisciplinary field of Systems Biology ( ), where biologists, chemists, engineers, mathematicians, physicists, and computer scientists have been trying to grapple with assembling these pieces into broader schemes, from the level of gene expression to the more complex levels of cell, tissue, and organism function. This issue of the STKE explores how a new generation of analytical tools and modeling is helping to break ground in understanding complex cellular signaling mechanisms. A Perspective by Chakraborty ([http:// http://www.stke.org/cgi/content/abstract/OC_sigtrans;2002/122/pe10][1]) reveals how quantitative analysis of immunological synapse formation, through mathematical modeling, has provided a mechanistic framework that explains the spatiotemporal dynamics of this important cell-cell adhesion complex and T cell signaling platform. Such an analysis has also generated new hypotheses about how early signaling events prepare T cells for generating synapses that produce specific cellular functions, such as cytokine production and T cell-mediated killing. For additional insight into how immune cell function is regulated and the role of the immune synapses in T cell signaling, see the Reviews by Sedwick and Altman ( ) and by Wange ( ). In Science , the application of engineering concepts to biological questions is the topic of the review by Csete and Doyle ( ). Similarities between the design of electronic circuits and cellular signaling pathways and how this has driven the development of sophisticated cell simulation software is the topic of the Perspective by Lok ( ). Tools that examine the structure and dynamics of signaling networks, based on knowledge of component connections and their kinetics relationships (signal propagation), are described [also see Modeling Tools ( )] in the ST on the Web section of the STKE). These tools can be used to help predict testable signaling schemes. As reported by Ferrell ( ) in an STKE Perspective from the Archives, computer simulations also indicate that scaffold proteins may be the critical determinants of a signaling pathway's output, a model that awaits experimental evidence. Integrating these various "parts" of information into "whole" biological schemes still depends on having basic and accurate parts information in hand. Genomics has given rise to proteomics, and as Ashman et al . ( ) point out in an STKE Perspective, understanding how protein-protein interactions integrate into signaling pathways and more global protein interaction networks is still at the heart of grasping biological complexity. The "Physiome," as described by Noble ( ) in Science , may represent the ultimate assembly of parts into a whole, as cellular and whole organ models of cardiac cells and the heart are being constructed through computer modeling. Such efforts may demonstrate the pathophysiological relevance of specific cardiac cell signaling pathways, such as those described in the STKE Review by Xiao ( ). Featured in This Focus Issue on Systems Biology Related Resources at STKE [1]: http://www.stke.org/cgi/content/abstract/OC_sigtrans;2002/122/pe10