Publications
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ORCID: 0000-0001-5574-5809
2024
Fast, multicolour optical sectioning over extended fields of view with Patterned Illumination and machine learning
E. N. Ward*, R. M. McClelland*, J. R. Lamb, R. Rubio-Sánchez, C. N. Christensen, B. Mazumder, S. Kapsiani, L. Mascheroni, L. Di Michele, G. S. Kaminski Schierle, C. F. Kaminski, Biomed. Opt. Express, 15(2), 1074 (2024)
We introduce a method that combines machine learning with structured illumination for optical sectioning and reconstruction of fluorescent specimens. We show that the technique allows for fast, 3D, and multicolour imaging of biological and biomimetic systems achieving resolution comparable to confocal microscopy.
2023
The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes
F. Raguseo, A. Huyghebaert, J. Li, R. Balendra, M. P. Howe, Y. Wang, D. M. Vadukul, D. Tanase, T. E. Maher, L. Malouf, R. Rubio-Sánchez, F. A. Aprile, Y. Elani, R. Patani‡, L. Di Michele‡, and M. Di Antonio‡, Nat. Commun. 14, 8272 (2023)
We explore the tendency of DNA and RNA hexanucleotide expansion repeats to form condensates in the absence of proteins. We find that amorphous aggregates emerge in physiologically relevant conditions for both DNA and RNA molecules. Aggregates are underpinned by non-canonical G-quadruplex structures, which provides a new avenue for targeting and drug development.
DNA-Origami Line-actants Control Domain Organisation and Fission in Synthetic Membranes
R. Rubio-Sánchez‡, B. M. Mognetti, P. Cicuta, and L. Di Michele‡, J. Am. Chem. Soc. 145, 11265 (2023)
We introduce the first line-active agents constructed from DNA nanostructures, which accumulate at the boundaries between co-existing lipid domains in synthetic membranes. We apply our DNA-Origami Line-Actants (DOLAs) to stabilise lipid domains against coalesce and to facilitate fission of lipid domains, demonstrating control over the two- and three-dimensional morphology of lipid membranes in synthetic cells.
Interplay of the mechanical and structural properties of DNA nanostructures determines their electrostatic interactions with lipid membranes
D. Morzy, C. Tekin, V. Caroprese, R. Rubio-Sánchez, L. Di Michele, and M. M. Bastings, Nanoscale 15, 2849 (2023)
We explore the influence of DNA nanostructure flexibility and size on DNA-lipid interactions facilitated by gel-phases and cation-mediated briding, showing that stiffer and bigger nanostructures bind more readily to gel membranes
2022
DNA-Based Optical Quantification of Ion Transport across Giant Vesicles
M. Fletcher, J. Zhu, R. Rubio-Sánchez, S. E. Sandler, K. Al Nahas, L. Di Michele, U.F. Keyser, and R. Tivony, ACS Nano 16, 17128 (2022)
We propose a DNA-based potassium sensor reliant on G-quadruplexes. We apply our biosensor and microfluidics to quantify the spontaneous transport of cations across synthetic lipid membranes in liposome populations, finding differences in transport rates between vesicle production techniques.
Editorial for “Special Issue on the 2019 and 2020 iGEM proceedings”
R. Rubio-Sánchez, Synth. Syst. Biotechnol. 7, 878 (2022)
I discuss the immense potential that the field of Synthetic Biology has for societal impact. Given its educational and hands-on approach, iGEM introduces young researchers to a vibrant and collaborative community, which enables the delivery of important research. I delve into some of the advances of the field facilitated by iGEM projects, now published in a 12-article collection in this Special Issue.
2021
iGEM comes of age: trends in its research output
A. K. Jainarayan‡, A. Galanis, A. Sreejith, S. Suresh, A. M. Nakara, G. E. Kundlatsch, and R. Rubio-Sánchez‡, Nat. Biotechnol. 39, 1599 (2021)
We explore the research output, in the form of publications and pre-printed manuscripts, of the International Genetically Engineered Machine (iGEM) competiton. We found that, between 2004—2021, more than 100 manuscripts with roots in iGEM projects have been published. Owing to the versatile and cross-disciplinary nature of the competition, these contributions fit in the wider field of Synthetic Biology advancing fronts as diverse as manufacturing, environmental, and biomedical sciences. This work was done as part of the Academia & Research Steering Group at iGEM Community
Amphiphilic DNA nanostructures for bottom-up synthetic biology
R. Rubio-Sánchez*, G. Fabrini*, P. Cicuta, and L. Di Michele, Chem. Commun. 57, 12725 (2021)
We discuss the current advances on engineering synthetic cells using amphiphilic DNA nano-devices. We focus on exploiting DNA to impart functionality to synthetic lipid membranes as well as on artificial cell implementations reliant on membrane-less compartments assembled from amphiphilic DNA building blocks.
Thermally Driven Membrane Phase Transitions Enable Content Reshuffling in Primitive Cells
R. Rubio-Sánchez, D. K. O´Flaherty, A. Wang, F. Coscia, G. Petris, L. Di Michele, P. Cicuta, and C. Bonfio, J. Am. Chem. Soc. 143, 16589 (2021)
We show pH changes, induced by thermal fluctuations, drive phase transitions in prebiotically-relevant lipid membranes. We propose a content reshuffling pathway that exploits reversible conversions between bilayer and oil phases, through which “daughter” protocells can emerge with reconstituted functionality from non-functional “parental” content.
Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria Entrapment
M. Walczak, R. A. Brady, L. Mancini, C. Contini, R. Rubio-Sánchez, W. T. Kaufhold, P. Cicuta, and L. Di Michele, Nat. Commun. 12, 4743 (2021)
We introduce a platform to construct DNA-based nanoparticles self-assembled from amphiphilic DNA nanostructures. Exploiting particle core-shell architecture, we expose hydrophobic pockets in response to chemical cues, which allows to permeabilise and disrupt lipid membranes, and also to capture bacteria, paving the way for new antimicrobial solutions.
Cations Regulate Membrane Attachment and Functionality of DNA Nanostructures
D. Morzy*, R. Rubio-Sánchez*, H. Joshi*, A. Aksimentiev‡, L. Di Michele‡, U.F. Keyser‡, J. Am. Chem. Soc. 143, 7358 (2021)
We explore the influence of cations and lipid phase on DNA-lipid interactions, finding that unmodified DNA duplexes bind gel-phase membranes through cation-mediated bridging. We engineer a cation-responsive DNA nano-machine to facilitate lipid transport between membrane leaflets, similar to scramblase enzymes.
A Modular, Dynamic, DNA-based Platform for Regulating Cargo Distribution and Transport between Lipid Domains
R. Rubio-Sánchez, S. E. Barker, M. Walczak, P. Cicuta, and L. Di Michele, Nano Lett. 21, 2800 (2021)
We introduce a dynamic strategy for controlling the lateral distribution of membrane inclusions along the surface of phase-separating liposomes with simple DNA nanostructures. Our approach allows for positioning and transporting cargoes between lipid domains in synthetic-cell membranes, reminiscent of the dynamic control over membrane receptor localisation at the cell-surface of biological cells.
Roger Rubio Sánchez 