Publications


Small molecule signals that direct the route of a molecular cargo.

Small 8 (2012) 3593-3597

RA Muscat, J Bath, AJ Turberfield

The route taken by a DNA cargo on a branched track can be controlled by the small molecule adenosine using a pair of aptamers that reciprocally block and unblock branches of the track in response to adenosine binding.


Sequence-specific synthesis of macromolecules using DNA-templated chemistry.

Chem Commun (Camb) 48 (2012) 5614-5616

PJ Milnes, ML McKee, J Bath, L Song, E Stulz, AJ Turberfield, RK O'Reilly

Using a strand exchange mechanism we have prepared, by DNA templated chemistry, two 10-mers with defined and tunable monomer sequences. An optimized reaction protocol achieves 85% coupling yield per step, demonstrating that DNA-templated chemistry is a powerful tool for the synthesis of macromolecules with full sequence control.


Programmable one-pot multistep organic synthesis using DNA junctions.

J Am Chem Soc 134 (2012) 1446-1449

ML McKee, PJ Milnes, J Bath, E Stulz, RK O'Reilly, AJ Turberfield

A system for multistep DNA-templated synthesis is controlled by the sequential formation of DNA junctions. Reactants are attached to DNA adapters which are brought together by hybridization to DNA template strands. This process can be repeated to allow sequence-controlled oligomer synthesis while maintaining a constant reaction environment, independent of oligomer length, at each reaction step. Synthesis can take place in a single pot containing all required reactive monomers. Different oligomers can be synthesized in parallel in the same vessel, and the products of parallel synthesis can be ligated, reducing the number of reaction steps required to produce an oligomer of a given length.


A DNA network as an information processing system

International Journal of Molecular Sciences 13 (2012) 5125-5137

CC Santini, J Bath, AJ Turberfield, AM Tyrrell

Biomolecular systems that can process information are sought for computational applications, because of their potential for parallelism and miniaturization and because their biocompatibility also makes them suitable for future biomedical applications. DNA has been used to design machines, motors, finite automata, logic gates, reaction networks and logic programs, amongst many other structures and dynamic behaviours. Here we design and program a synthetic DNA network to implement computational paradigms abstracted from cellular regulatory networks. These show information processing properties that are desirable in artificial, engineered molecular systems, including robustness of the output in relation to different sources of variation. We show the results of numerical simulations of the dynamic behaviour of the network and preliminary experimental analysis of its main components. © 2012 by the authors.


Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics): Preface

, 2012

D Stefanovic, A Turberfield


Remote toehold: a mechanism for flexible control of DNA hybridization kinetics.

J Am Chem Soc 133 (2011) 2177-2182

AJ Genot, DY Zhang, J Bath, AJ Turberfield

Hybridization of DNA strands can be used to build molecular devices, and control of the kinetics of DNA hybridization is a crucial element in the design and construction of functional and autonomous devices. Toehold-mediated strand displacement has proved to be a powerful mechanism that allows programmable control of DNA hybridization. So far, attempts to control hybridization kinetics have mainly focused on the length and binding strength of toehold sequences. Here we show that insertion of a spacer between the toehold and displacement domains provides additional control: modulation of the nature and length of the spacer can be used to control strand-displacement rates over at least 3 orders of magnitude. We apply this mechanism to operate displacement reactions in potentially useful kinetic regimes: the kinetic proofreading and concentration-robust regimes.


Direct observation of stepwise movement of a synthetic molecular transporter.

Nat Nanotechnol 6 (2011) 166-169

SFJ Wickham, M Endo, Y Katsuda, K Hidaka, J Bath, H Sugiyama, AJ Turberfield

Controlled motion at the nanoscale can be achieved by using Watson-Crick base-pairing to direct the assembly and operation of a molecular transport system consisting of a track, a motor and fuel, all made from DNA. Here, we assemble a 100-nm-long DNA track on a two-dimensional scaffold, and show that a DNA motor loaded at one end of the track moves autonomously and at a constant average speed along the full length of the track, a journey comprising 16 consecutive steps for the motor. Real-time atomic force microscopy allows direct observation of individual steps of a single motor, revealing mechanistic details of its operation. This precisely controlled, long-range transport could lead to the development of systems that could be programmed and routed by instructions encoded in the nucleotide sequences of the track and motor. Such systems might be used to create molecular assembly lines modelled on the ribosome.


Peptidomimetic bond formation by DNA-templated acyl transfer.

Org Biomol Chem 9 (2011) 1661-1666

ML McKee, AC Evans, SR Gerrard, RK O'Reilly, AJ Turberfield, E Stulz

The efficiencies of DNA-templated acyl transfer reactions between a thioester modified oligonucleotide and a series of amine and thiol based nucleophiles are directly compared. The reactivity of the nucleophile, reaction conditions (solvent, buffer, pH) and linker length all play important roles in determining the efficiency of the transfer reaction. Careful optimisation of the system enables the use of DNA-templated synthesis to form stable peptide-like bonds under mild aqueous conditions close to neutral pH.


A programmable molecular robot.

Nano Lett 11 (2011) 982-987

RA Muscat, J Bath, AJ Turberfield

We have developed a programmable and auton-omous molecular robot whose motion is fueled by DNA hybridization. Instructions determining the path to be followed are programmed into the fuel molecules, allowing precise control of cargo motion on a branched track.


DNA nanotechnology: geometrical self-assembly.

Nat Chem 3 (2011) 580-581

AJ Turberfield


DNA cage delivery to mammalian cells.

ACS Nano 5 (2011) 5427-5432

AS Walsh, H Yin, CM Erben, MJA Wood, AJ Turberfield

DNA cages are nanometer-scale polyhedral structures formed by self-assembly from synthetic DNA oligonucleotides. Potential applications include in vivo imaging and the targeted delivery of macromolecules into living cells. We report an investigation of the ability of a model cage, a DNA tetrahedron, to enter live cultured mammalian cells. Cultured human embryonic kidney cells were treated with a range of fluorescently labeled DNA tetrahedra and subsequently examined using confocal microscopy and flow cytometry. Substantial uptake of tetrahedra into cells was observed both when the cells were treated with tetrahedra alone and when the cells were treated with a mixture of tetrahedra and a transfection reagent. Analysis of the subcellular localization of transfected tetrahedra using confocal microscopy and organelle staining indicates that the cages are located in the cytoplasm. FRET experiments indicate that the DNA cages remain substantially intact within the cells for at least 48 h after transfection. This is a first step toward the use of engineered DNA nanostructures to deliver and control the activity of cargoes within cells.


DNA-templated protein arrays for single-molecule imaging.

Nano Lett 11 (2011) 657-660

DN Selmi, RJ Adamson, H Attrill, AD Goddard, RJC Gilbert, A Watts, AJ Turberfield

Single-particle electron cryomicroscopy permits structural characterization of noncrystalline protein samples, but throughput is limited by problems associated with sample preparation and image processing. Three-dimensional density maps are reconstructed from high resolution but noisy images of individual molecules. We show that self-assembled DNA nanoaffinity templates can create dense, nonoverlapping arrays of protein molecules, greatly facilitating data collection. We demonstrate this technique using a G-protein-coupled membrane receptor, a soluble G-protein, and a signaling complex of both molecules.


Remote toehold: A mechanism for flexible control of DNA hybridization kinetics

Journal of the American Chemical Society 133 (2011) 2177-2182

AJ Genot, DY Zhang, J Bath, AJ Turberfield

Hybridization of DNA strands can be used to build molecular devices, and control of the kinetics of DNA hybridization is a crucial element in the design and construction of functional and autonomous devices. Toehold-mediated strand displacement has proved to be a powerful mechanism that allows programmable control of DNA hybridization. So far, attempts to control hybridization kinetics have mainly focused on the length and binding strength of toehold sequences. Here we show that insertion of a spacer between the toehold and displacement domains provides additional control: modulation of the nature and length of the spacer can be used to control strand-displacement rates over at least 3 orders of magnitude. We apply this mechanism to operate displacement reactions in potentially useful kinetic regimes: the kinetic proofreading and concentration-robust regimes. © 2011 American Chemical Society.


Reversible logic circuits made of DNA.

J Am Chem Soc 133 (2011) 20080-20083

AJ Genot, J Bath, AJ Turberfield

We report reversible logic circuits made of DNA. The circuits are based on an AND gate that is designed to be thermodynamically and kinetically reversible and to respond nonlinearly to the concentrations of its input molecules. The circuits continuously recompute their outputs, allowing them to respond to changing inputs. They are robust to imperfections in their inputs.


A geometrical allosteric DNA switch

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 6079 LNCS (2010) 189-

AJ Genot, J Bath, AJ Turberfield


Multistep DNA-templated reactions for the synthesis of functional sequence controlled oligomers.

Angew Chem Int Ed Engl 49 (2010) 7948-7951

ML McKee, PJ Milnes, J Bath, E Stulz, AJ Turberfield, RK O'Reilly


Observation of Structural Changes on Activation of the NTS1 G-Protein-Coupled Receptor on DNA-Templated Protein Arrays by cryo-EM

BIOPHYSICAL JOURNAL 98 (2010) 418A-418A

DN Selmi, H Attrill, A Watts, RJC Gilbert, AJ Turberfield


A Geometrical Allosteric DNA Switch

UNCONVENTIONAL COMPUTATION, PROCEEDINGS 6079 (2010) 189-189

AJ Genot, J Bath, AJ Turberfield


Sequential DNA templated reactions towards the synthesis of ordered oligomers

7th Annual Conference on Foundations of Nanoscience: Self-Assembled Architectures and Devices, FNANO 2010 (2010) 71-72

P Milnes, M McKee, J Bath, E Stulz, A Turberfield, R O'Reilly


A cascade of DNA strand displacements using toehold-mediated exchange

7th Annual Conference on Foundations of Nanoscience: Self-Assembled Architectures and Devices, FNANO 2010 (2010) 55-

P Lally, J Bath, AJ Turberfield

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