Thursday, April 8, 2010

Numbers on the edges: A simplified and scalable method for quantifying the Gene Regulation Function


  1. Raul Fernandez-Lopez, 
  2. Irene del Campo, 
  3. Raúl Ruiz, 
  4. Val Lanza, 
  5. Luis Vielva, 
  6.  Fernando de la Cruz
    1. Abstract


      The gene regulation function (GRF) provides an operational description of a promoter behavior as a function of the concentration of one of its transcriptional regulators. Behind this apparently trivial definition lies a central concept in biological control: the GRF provides the input/output relationship of each edge in a transcriptional network, independently from the molecular interactions involved. Here we discuss how existing methods allow direct measurement of the GRF, and how several trade-offs between scalability and accuracy have hindered its application to relatively large networks. We discuss the theoretical and technical requirements for obtaining the GRF. Based on these requirements, we introduce a simplified and easily scalable method that is able to capture the significant parameters of the GRF. The GRF is able to predict the behavior of a simple genetic circuit, illustrating how addressing the quantitative nature of gene regulation substantially increases our comprehension on the mechanisms of gene control.