Biomathematics - Canalization: a fundamental design principle of gene regulatory networks

The mathematical objective of the project is to derive mathematical principles governing network dynamics of gene regulatory networks, focusing on the role of so-called microRNAs, that is, regulatory elements in the genome that act through certain types of feedforward loops. They are hypothesized to confer robustness on gene regulatory networks, stabilizing their dynamics in the face of extrinsic and intrinsic noise and other stochastic features. Thus, their action represents a potential law of biology for the stabilization of organismal phenotype in the face of uncertainty. While the role of many individual microRNAs in gene regulatory networks has been studied experimentally, it is very difficult or impossible to study their collective, genome-scale role, especially from the point of view of deriving general features of the dynamics of the genome-scale transcriptional networks in mammals. Note that there are estimated to be thousands of microRNAs in the genome, each of which can regulate potentially hundreds of transcription factors. This leaves mathematical modeling as one of a few options, combined with genome-scale information on the human genome, e.g., features of transcriptional networks and microRNA features.