ArticleJournal of biological engineering2019
The engineering principles of combining a transcriptional incoherent feedforward loop with negative feedback.
Article in Journal of biological engineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed.
- Epigenome regulators imbue a single eukaryotic promoter with diverse gene expression dynamics.iScience · 2026Article
- Remote control of AMPK via extracellular adenosine controls tissue growth.Nature cell biology · 2025Article
- Tunable, proteolytic dosage control of CRISPR-Cas systems enables precise gene therapy for dosage sensitive disorders.bioRxiv : the preprint server for biology · 2025Article
- Dual nature of type I interferon responses and feedback regulations by SOCS1 dictate malaria mortality.Journal of advanced research · 2025Article
- Receptor kinase pathway signal tuning through a nontranscriptional incoherent feedforward loop.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- GnuR Represses the Expression of Glucose and Gluconate Catabolism in Pseudomonas putida KT2440.Microbial biotechnology · 2024Article
- Optimal performance objectives in the highly conserved bone morphogenetic protein signaling pathway.NPJ systems biology and applications · 2024Article
- A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network.Circulation · 2024Article
- Performing in spite of starvation: How Saccharomyces cerevisiae maintains robust growth when facing famine zones in industrial bioreactors.Microbial biotechnology · 2023Article
- Network inference from perturbation time course data.NPJ systems biology and applications · 2022Article
- Understanding the Effects of Age and T-Cell Differentiation on COVID-19 Severity: Implicating a Fas/FasL-mediated Feed-Forward Controller of T-Cell Differentiation.Frontiers in immunology · 2022Article
- Design and Evaluation of Synthetic RNA-Based Incoherent Feed-Forward Loop Circuits.Biomolecules · 2021Article
- Glucocorticoid-Mediated Developmental Programming of Vertebrate Stress Responsivity.Frontiers in physiology · 2021Review
- Article
- Rewiring of gene expression in circulating white blood cells is associated with pregnancy outcome in heifers (Bos taurus).Scientific reports · 2020Article
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Abstract
backgroundRegulation of gene expression is of paramount importance in all living systems. In the past two decades, it has been discovered that certain motifs, such as the feedforward motif, are overrepresented in gene regulatory circuits. Feedforward loops are also ubiquitous in process control engineering, and are nearly always structured so that one branch has the opposite effect of the other, which is a structure known as an "incoherent" feedforward loop in biology. In engineered systems, feedforward control loops are subject to several engineering constraints, including that (1) they are finely-tuned so that the system returns to the original steady state after a disturbance occurs (perfect adaptation), (2) they are typically only implemented in the combination with negative feedback, and (3) they can greatly improve the stability and dynamical characteristics of the conjoined negative feedback loop. On the other hand, in biology, incoherent feedforward loops can serve many purposes, one of which may be perfect adaptation. It is an open question as to whether those that achieve perfect adaptation are subject to the above engineering principles.
resultsWe analyzed an incoherent feedforward gene regulatory motif from the standpoint of the above engineering principles. In particular, we showed that an incoherent feedforward loop Type 1 (I1-FFL), from within a gene regulatory circuit, can be finely-tuned for perfect adaptation after a stimulus, and that the robustness of this behavior is increased by the presence of moderate negative feedback. In addition, we analyzed the advantages of adding a feedforward loop to a system that already operated under negative feedback, and found that the dynamical properties of the combined feedforward/feedback system were superior.
conclusionsOur analysis shows that many of the engineering principles used in engineering design of feedforward control are also applicable to feedforward loops in biological systems. We speculate that principles found in other domains of engineering may also be applicable to analogous structures in biology.
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