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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{Smith:2024:10.1039/d4nr00542b,
author = {Smith, F and Goetz, J and Jurinovic, K and Stevens, M and Ouldridge, T},
doi = {10.1039/d4nr00542b},
journal = {Nanoscale},
pages = {17624--17637},
title = {Strong sequence-dependence in RNA/DNA hybrid strand displacement kinetics},
url = {http://dx.doi.org/10.1039/d4nr00542b},
volume = {16},
year = {2024}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Strand displacement reactions underlie dynamic nucleic acid nanotechnology. The kinetic and thermodynamic features of DNA-based displacement reactions are well understood and well predicted by current computational models. By contrast, understanding of RNA/DNA hybrid strand displacement kinetics is limited, restricting the design of increasingly complex RNA/DNA hybrid reaction networks with more tightly regulated dynamics. Given the importance of RNA as a diagnostic biomarker, and its critical role in intracellular processes,this shortfall is particularly limiting for the development of strand displacement-based therapeutics and diagnostics. Herein, we characterise 22 RNA/DNA hybrid strand displacement systems, alongside 11 DNA/DNA systems, varying a range of common design parameters including toehold length and branch migration domain length. We observe the differences in stability between RNA-DNA hybrids and DNA-DNA duplexes have large effects on strand displacement rates, with rates for equivalent sequences differing by up to 3 orders of magnitude. Crucially, however, this effect is strongly sequence-dependent, with RNA invaders strongly favoured in a system with RNA strands of high purine content, and disfavoured in a system when the RNA strands have low purine content. These results lay the groundwork for more general design principles, allowing for creation of de novo reaction networks with novel complexity while maintaining predictable reaction kinetics.
AU  - Smith,F
AU  - Goetz,J
AU  - Jurinovic,K
AU  - Stevens,M
AU  - Ouldridge,T
DO  - 10.1039/d4nr00542b
EP  - 17637
PY  - 2024///
SN  - 2040-3364
SP  - 17624
TI  - Strong sequence-dependence in RNA/DNA hybrid strand displacement kinetics
T2  - Nanoscale
UR  - http://dx.doi.org/10.1039/d4nr00542b
UR  - https://pubs.rsc.org/en/content/articlelanding/2024/nr/d4nr00542b
UR  - http://hdl.handle.net/10044/1/114071
VL  - 16
ER  -