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Reconstructing regulatory circuits: lessons from immune cells (92.1)
Author(s) -
Regev Aviv
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.92.1
Subject(s) - computer science , electronic circuit , key (lock) , computational biology , immune system , systems biology , computational model , neuroscience , biology , artificial intelligence , physics , immunology , computer security , quantum mechanics
Molecular circuits are the information processing devices of cells and organisms, transforming extra‐ and intra‐cellular signals into coherent cellular responses. While there has been hope that genomic approaches would make it possible to systematically reconstruct circuitry, genomic studies have largely been observational and rarely involve large‐scale testing and refinement of models. We develop a systematic computational and experimental approach to reconstruct circuitry by profiling the circuit’s output or internal state along a relevant time course, learning a computational model that explains the observed data, perturbing every key component proposed by our model, and repeating the process, until data and model converge. All circuits are dynamic, and rewire in response to perturbation, at time scales from minutes to eons, as cells respond to new environmental conditions, differentiate, or evolve. We focus on a carefully selected model system at each time scale, from minutes to eons. In this talk, I will focus on describing our studies in immune cells, especially DCs and T cells, showing how we can dissect transcriptional and signaling circuits and their functionality in key physiological responses.