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Research

Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology.

As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.

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  -