Imperial College London
Portrait Picture

Guy-Bart Stan

Faculty of Engineering, Department of Bioengineering

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 6375g.stan Website

 
 
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Location

 

B703Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cella:2023:nar/gkad151,
author = {Cella, F and Perrino, G and Tedeschi, F and Viero, G and Bosia, C and Stan, G-B and Siciliano, V},
doi = {nar/gkad151},
journal = {Nucleic Acids Research},
pages = {3452--3464},
title = {MIRELLA: a mathematical model explains the effect of microRNA-mediated synthetic genes regulation on intracellular resource allocation},
url = {http://dx.doi.org/10.1093/nar/gkad151},
volume = {51},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Competition for intracellular resources, also known as gene expression burden, induces coupling between independently co-expressed genes, a detrimental effect on predictability and reliability of gene circuits in mammalian cells. We recently showed that microRNA (miRNA)-mediated target downregulation correlates with the upregulation of a co-expressed gene, and by exploiting miRNAs-based incoherent-feed-forward loops (iFFLs) we stabilise a gene of interest against burden. Considering these findings, we speculate that miRNA-mediated gene downregulation causes cellular resource redistribution. Despite the extensive use of miRNA in synthetic circuits regulation, this indirect effect was never reported before. Here we developed a synthetic genetic system that embeds miRNA regulation, and a mathematical model, MIRELLA, to unravel the miRNA (MI) RolE on intracellular resource aLLocAtion. We report that the link between miRNA-gene downregulation and independent genes upregulation is a result of the concerted action of ribosome redistribution and ‘queueing-effect’ on the RNA degradation pathway. Taken together, our results provide for the first time insights into the hidden regulatory interaction of miRNA-based synthetic networks, potentially relevant also in endogenous gene regulation. Our observations allow to define rules for complexity- and context-aware design of genetic circuits, in which transgenes co-expression can be modulated by tuning resource availability via number and location of miRNA target sites.
AU  - Cella,F
AU  - Perrino,G
AU  - Tedeschi,F
AU  - Viero,G
AU  - Bosia,C
AU  - Stan,G-B
AU  - Siciliano,V
DO  - nar/gkad151
EP  - 3464
PY  - 2023///
SN  - 0305-1048
SP  - 3452
TI  - MIRELLA: a mathematical model explains the effect of microRNA-mediated synthetic genes regulation on intracellular resource allocation
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkad151
UR  - https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad151/7076485
UR  - http://hdl.handle.net/10044/1/102984
VL  - 51
ER  -
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