Networks in the Life Sciences – Genomics, Proteomics and Systems Biology
14th EMBL PhD Symposium

25th–27th October 2012

Speaker: Prof. Dr. Alex Hoffmann

  • University of California, San Diego

Background

Alex Hoffmann Professor of chemistry and biochemistry at the University of California, San Diego, Alex Hoffmann is the director of the graduate programme in bioinformatics and systems biology and principal investigator of the signalling systems laboratory. His group takes a multi-scale approach, from cell population to molecular signal regulatory networks (SRN) and attempts to achieve a predictive understanding of both the innate and adaptive immune response.

Talk: Combinatorial and dynamic control logic within pathogen-responsive gene regulatory networks

Studies of the cellular responses to pathogens have identified several primary response transcription factors (TFs), that are activated in stimulus-specific combinations and temporal profiles. To understand how dynamic activities may combine to produce the regulatory logic of pathogen-responsive gene expression, we utilized mathematical modeling to guide the analysis of a multi-dimensional expression dataset of 714 transcripts induced by bacterial endotoxin. We found that gene clusters are controlled by signal-responsive TFs either singly or sequentially in or gates, but that further specification of expression programs is mediated by constitutive and signal-responsive mRNA halflife control. The results reveal that mRNA halflife control is responsible for decoding not only stimulus-responsive TF dynamics, but also pathway combinatorics. We surmise that predictive models of gene regulatory networks (GRNs) cannot be based on chromatin-associated events alone but must include non-nuclear control mechanisms as well. Our work begins to delineate how intra-cellular combinatorial and dynamic signals that encode information about the extra-cellular stimulus are decoded through specific mechanisms within GRNs.