The Alpha Project, a model system for systems biology research

RICHARD YU; ORNA RESNEKOV; PIA ABOLA; STEVE ANDREWS; KIRSTEN BENJAMIN; JEHOSHUA BRUCK; IAN BURBULIS; ALEJANDRO COLMAN-LERNER; DREW ENDY; ANDREW GORDON; MARK HALL; LARRY LOK; ROBERT MAXWELL; GUSTAVO PESCE; EDUARD SERRA; RICHARD SMITH; TY THOMSON; ANNIE TSONG; ROGER BRENT

IET Systems Biology

Institution of Engineering and Technology

Lugar: London, UK; Año: 2008

1751-8849

A major goal of systems biology is understanding how genome-encoded parts interact to produce quantitative phenotypes. The Alpha Project is a medium-scale, interdisciplinary systems biology effort toward achieving this goal by understanding the fundamental quantitative behaviors of a prototypic signal transduction pathway, the yeast pheromone response system in Saccharomyces cerevisiae. This effort distinguishes itself from some systems biology projects in that it studies a tightlybounded and well-characterized system that is easily modified by genetic means, and focuses on a discrete number of tractable and understandable quantitative behaviors. During the project, we have developed both tools to measure the appropriate data and models at appropriate levels of detail for studying these quantitative behaviors. We also have developed transportable experimental and conceptual tools that we believe will be useful for understanding other signaling systems. In particular, we have begun to interpret system behaviors and their underlying molecular mechanisms through the lens of information transmission, a principal function of signaling systems. By identifying key quantitative behaviors, measuring the important quantities, and developing conceptual abstractions, this effort complements other efforts that focus on making comprehensive, detailed chemical reaction network models. Our experience to date shows that focused interdisciplinary studies, in the context of well-articulated abstractions of system function and appropriate analytical frameworks, can lead to real progress, and may provide a productive template for system biology investigations of other cellular systems.