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

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Baker MA (2016) Domain-swap polymerization drives the self-assembly of the bacterial flagellar motor. in Nature structural & molecular biology

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Bath J (2009) Mechanism for a directional, processive, and reversible DNA motor. in Small (Weinheim an der Bergstrasse, Germany)

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Carstairs HM (2009) DNA monofunctionalization of quantum dots. in Chembiochem : a European journal of chemical biology

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Costa Santini C (2013) A clocked finite state machine built from DNA. in Chemical communications (Cambridge, England)

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Crawford R (2013) Non-covalent single transcription factor encapsulation inside a DNA cage. in Angewandte Chemie (International ed. in English)

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Dannenberg F (2015) Modelling DNA origami self-assembly at the domain level. in The Journal of chemical physics

 
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