Molecular Motors
Lead Research Organisation:
University of Oxford
Department Name: Oxford Physics
Abstract
Molecular motors are used by cells to control their internal layout, to transport cargoes, to change shape and to move. We will construct artificial molecular machines in order to study the mechanisms and functions of molecular motors, to understand their physical principles, and to develop new technologies for nanoscale molecular systems. The project is based on techniques for molecular-scale construction using DNA. DNA is a wonderful material with which to build: by exploiting the base-pairing interactions that hold together the DNA double helix, it is possible to control the way in which short, synthetic strands of DNA assemble to form complex three-dimensional objects. It is even possible to make these structures move. We will create all-synthetic molecular motors from DNA, using design principles based on the mechanisms of motor proteins. We will also create hybrid machines consisting of natural motor proteins linked to artificial DNA templates. We will use these structures to perform functions that are inspired by the molecular machinery of the cell and to explore the ways in which motors and their tracks can be designed to interact to create complex structures and movements. This project we will provide career development opportunities and interdisciplinary training in research at the physics / life sciences interface for postdoctoral researchers and graduate students.
Publications
Baker MA
(2016)
Domain-swap polymerization drives the self-assembly of the bacterial flagellar motor.
in Nature structural & molecular biology
Baker MAB
(2018)
Dimensions and Global Twist of Single-Layer DNA Origami Measured by Small-Angle X-ray Scattering.
in ACS nano
Bath J
(2009)
Mechanism for a directional, processive, and reversible DNA motor.
in Small (Weinheim an der Bergstrasse, Germany)
Boemo MA
(2016)
The Formal Language and Design Principles of Autonomous DNA Walker Circuits.
in ACS synthetic biology
Carstairs HM
(2009)
DNA monofunctionalization of quantum dots.
in Chembiochem : a European journal of chemical biology
Costa Santini C
(2013)
A clocked finite state machine built from DNA.
in Chemical communications (Cambridge, England)
Crawford R
(2013)
Non-covalent single transcription factor encapsulation inside a DNA cage.
in Angewandte Chemie (International ed. in English)
Dannenberg F
(2015)
Modelling DNA origami self-assembly at the domain level.
in The Journal of chemical physics
Dannenberg F
(2014)
DNA walker circuits: computational potential, design, and verification
in Natural Computing
| Description | Molecular motors are used by cells to control their internal layout, to transport cargoes, to change shape and to move. We are constructing artificial molecular machines in order to study the mechanisms and functions of molecular motors, to understand their physical principles, and to develop new technologies for nanoscale molecular systems. The project is based on techniques for molecular-scale construction using DNA. DNA is a wonderful material with which to build: by exploiting the base-pairing interactions that hold together the DNA double helix, it is possible to control the way in which short, synthetic strands of DNA assemble to form complex three-dimensional objects. It is even possible to make these structures move. We have created all-synthetic molecular motors from DNA, using design principles based on the mechanisms of natural motor proteins. We have also created hybrid machines consisting of natural motor proteins linked to artificial DNA templates which can be controlled by molecular signals encoded in short strands of DNA. We are using these structures to perform functions that are inspired by the molecular machinery of the cell and to explore the ways in which motors and their tracks can be designed to interact to create complex structures and movements. We have extended this work to investigate new ways to design interacting molecular systems to provide control of kinetic processes - these have applications both in the assembly and operation of synthetic molecular machinery and of molecular systems that compute. We are currently studying ways in which synthetic molecular motors can be used to drive molecular production lines, leading to new technologies for, e.g., atomically precise manufacturing and drug discovery. |
| Exploitation Route | Our research into molecular motors contributes to a wide range of exciting research into the construction of functional biomimetic devices and systems, i.e., synthetic biology from the bottom up. Molecular motors are the key to the creation of multiscale systems in which molecular components govern structure and function at the micrometre scale and beyond. We and others are using synthetic molecular motors to drive molecular factories that can be programmed to link reactive molecules in defined sequences to create polymers. These have potential for the development of new drugs by selection from large combinatorial libraries. Many groups are studying related dynamic DNA robotic devices to be deployed as 'smart' drug delivery vehicles, integrating sensing, computation and actuation, and capable of carrying cargoes into cells and controlling their release. An exciting new development is the idea that motor-driven nanostructures could be used as molecular 3D printers, providing a completely new method for atomically precise manufacture. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | Our work on the development of dynamic DNA devices and molecular machinery has contributed to a huge growth in the international research community that studies DNA self-assembly. Practical applications of this revolutionary new technology are only now beginning to emerge, but promising directions include molecular manufacture and molecular electronics, drug discovery, drug delivery and structural biology. Evidence that the technological implications of this technology are being considered outside the academic sector includes a recently announced call for proposals (FOA) on Molecular Additive Manufacture by the US Department of Energy; this follows a workshop on DNA-based machinery for manufacturing attended by DOE representatives and AJT. |
| First Year Of Impact | 2009 |
| Sector | Other |
| Description | 14-ERASynBio BioOrigami |
| Amount | £415,854 (GBP) |
| Funding ID | BB/M005739/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 08/2017 |
| Description | Artificial synthesis of the bacterial flagellar motor with DNA nanostructures |
| Amount | $1,200,000 (USD) |
| Funding ID | RGP0030/2013 |
| Organisation | Human Frontier Science Program (HFSP) |
| Sector | Charity/Non Profit |
| Country | France |
| Start | 09/2013 |
| End | 08/2016 |
| Description | EScoDNA Marie Curie Initial Training Network |
| Amount | € 4,070,204 (EUR) |
| Funding ID | 317110 |
| Organisation | Marie Sklodowska-Curie Actions |
| Sector | Charity/Non Profit |
| Country | Global |
| Start | 02/2013 |
| End | 01/2017 |
| Description | Extending the Boundaries of Nucleic Acid Chemistry |
| Amount | £1,659,227 (GBP) |
| Funding ID | BB/J00054X/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2012 |
| End | 03/2017 |
| Description | Marie Sklodowska Curie Innovative Training Network |
| Amount | € 3,979,633 (EUR) |
| Funding ID | 765703 |
| Organisation | European Commission H2020 |
| Sector | Public |
| Country | Belgium |
| Start | 01/2018 |
| End | 12/2021 |
| Description | Molecular materials, sensors and circuits with nanometre resolution |
| Amount | £201,893 (GBP) |
| Funding ID | EP/I016651/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2010 |
| End | 04/2012 |
| Description | Royal Society Wolfson Research Merit Award |
| Amount | £100,000 (GBP) |
| Funding ID | WM110130 |
| Organisation | The Royal Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2012 |
| End | 03/2017 |
| Description | University of Oxford John Fell Fund |
| Amount | £72,096 (GBP) |
| Organisation | University of Oxford |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2017 |
| End | 09/2018 |
| Description | Arzhang |
| Organisation | University of Manchester |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Design and fabrication of DNA templates |
| Collaborator Contribution | Synthesis of conducting molecules |
| Impact | Programme grant outline application |
| Start Year | 2013 |
| Description | Arzhang |
| Organisation | University of Strathclyde |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Design and fabrication of DNA templates |
| Collaborator Contribution | Synthesis of conducting molecules |
| Impact | Programme grant outline application |
| Start Year | 2013 |
| Description | RC |
| Organisation | Marie Curie |
| Department | Marie Curie Research Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Joint research on kinesin biophysics and kinesin-DNA hybrid devices |
| Collaborator Contribution | Joint research on kinesin biophysics and kinesin-DNA hybrid devices |
| Impact | See outcomes of grants BBG0191181 and EP/G037930/1 Multidisciplinary: physics, molecular and cellular biology |
| Start Year | 2009 |
| Description | RC |
| Organisation | University of Warwick |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Joint research on kinesin biophysics and kinesin-DNA hybrid devices |
| Collaborator Contribution | Joint research on kinesin biophysics and kinesin-DNA hybrid devices |
| Impact | See outcomes of grants BBG0191181 and EP/G037930/1 Multidisciplinary: physics, molecular and cellular biology |
| Start Year | 2009 |
| Description | Z/W |
| Organisation | California Institute of Technology |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Joint research project on catalytic hybridization reactions. |
| Collaborator Contribution | Joint research project on catalytic hybridization reactions. |
| Impact | Engineering entropy-driven reactions and networks catalyzed by DNA D. Y. Zhang, A. J. Turberfield, B. Yurke and E. Winfree Science 318, 1121-1125 (2007) doi:10.1126/science.1148532 doi:10.1021/ja071493b The remote toehold, a mechanism for flexible control of DNA hybridization kinetics A. J. Genot, D. Y. Zhang, J. Bath and A. J. Turberfield J. Am. Chem. Soc. 133, 2177-2182 (2011) Patent WO2008097929-A2 Toehold exchange catalyst system for constructing and characterizing circuits that amplify nucleic acid signals, e.g. feed-forward cascade with quadratic kinetics, comprises substrate molecule, ligand molecules and catalyst molecule Multidisciplinary: Physics, Computer Science |
| Start Year | 2006 |
| Description | Cherwell 2014 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Discussion with sixth formers - particularly interested in cross-disciplinary aspect of research described School has departmental contact to arrange future speakers |
| Year(s) Of Engagement Activity | 2014 |
| Description | Marston 2014 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Questions about principles of self-assembly Talk to scout troop - enabled engagement with school-age children, many of whom would not normally come to a talk on science |
| Year(s) Of Engagement Activity | 2014 |
| Description | Oxfordshire Science Festival |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Engagement and discussion with a very wide age range. Engagment with members of public with a very wide range of backgrounds and interests. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Royal Society Summer Exhibition |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Lively interest from school children with a wide range of ages N/A |
| Year(s) Of Engagement Activity | 2012 |
| Description | WowHow |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Lively engagement with children of both primary and secondary age Schools asked for teaching materials |
| Year(s) Of Engagement Activity | 2012,2014 |