Software-controlled assembly of oligomers

Lead Research Organisation: University of Oxford
Department Name: Oxford Physics

Abstract

We propose to create a molecular machine that will build new materials under software control. The output of the machine will be chains of building blocks linked by covalent bonds. The machine is modular and is designed to accept many different building blocks, from small molecules to nanoparticles, with a wide range of physical and chemical properties. In order to drive its development we will concentrate on using it to create two target products: a molecular wire, capable of transporting energy and electrical charge, and a catalyst. Software control starts with specification by the end-user of a sequence of building blocks. The target sequence is encoded in an instruction tape which can be read by the machine: the tape is itself a molecule, a synthetic DNA oligomer. The target sequence of building blocks is automatically converted into a control sequence of DNA bases, and the tape is produced by commercial solid-phase synthesis. The job of the machine is to read the instruction tape and to form the bonds between building blocks in the specified sequence. Every component of this molecular factory is itself a molecule: our ambition is to develop the system to the point where it could be distributed to end users as chemicals in plastic vials.

Publications

10 25 50
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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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McKee ML (2010) Multistep DNA-templated reactions for the synthesis of functional sequence controlled oligomers. in Angewandte Chemie (International ed. in English)

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McKee ML (2012) Programmable one-pot multistep organic synthesis using DNA junctions. in Journal of the American Chemical Society

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McKee ML (2011) Peptidomimetic bond formation by DNA-templated acyl transfer. in Organic & biomolecular chemistry

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Milnes PJ (2012) Sequence-specific synthesis of macromolecules using DNA-templated chemistry. in Chemical communications (Cambridge, England)

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Muscat RA (2012) Small molecule signals that direct the route of a molecular cargo. in Small (Weinheim an der Bergstrasse, Germany)

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O'Reilly RK (2017) The Evolution of DNA-Templated Synthesis as a Tool for Materials Discovery. in Accounts of chemical research

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Santini CC (2012) A DNA network as an information processing system. in International journal of molecular sciences

 
Description We have investigated the creation of molecular machinery that will build new materials under software control. The designed output of the machine is a molecule consisting of chains of building blocks linked by covalent bonds. The machine is modular and is designed to accept many different building blocks, from small molecules to nanoparticles, with a wide range of physical and chemical properties. Software control starts with specification by the end-user of a sequence of building blocks. The target sequence is encoded in an instruction tape which can be read by the machine: the tape is itself a molecule, a synthetic DNA oligomer. The target sequence of building blocks is automatically converted into a control sequence of DNA bases, and the tape is produced by commercial solid-phase synthesis. The job of the machine is to read the instruction tape and to form the bonds between building blocks in the specified sequence. Every component of this molecular factory is itself a molecule: our ambition is to develop the system to the point where it could be distributed to end users as chemicals in plastic vials. In this project we have developed suitable building blocks and demonstrated that we can control the order in which they are assembled using programmable molecular systems made from DNA.
Exploitation Route To achieve their full potential impact, the ideas contained in this proposal will require research and development well beyond the scope of this proposal. In the initial stages of this project (covered by this proposal) the principal beneficiary has been the academic community - particularly in the field of molecular nanotechnology, also in synthetic biology. We anticipate that successful development of an intelligent molecular manufacturing processes will lead to industrial interest, particularly in the following sectors: pharmaceutical (enzyme inhibitors, cyclic peptides), chemical manufacturing (catalyst development) and electronic (optoelectronic components, electronic wires). Commercial adoption and development has the potential to contribute to the UK economy and to public health and standard of living, for example through innovations in drug development, manufacture and delivery, and in the development of novel prototyping and manufacturing techniques.
Sectors Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Our work on the development of DNA structures, and especially dynamic DNA devices and molecular machines, 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. We are continuing to develop systems for molecular manufacture based on synthetic molecular machinery in order to advance the very new field of molecular robotics and to create a new technology for molecular discovery based on combinatorial synthesis, selection and molecular evolution.
First Year Of Impact 2011
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 Critical Mass Award
Amount £2,340,288 (GBP)
Funding ID EP/P000479/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 11/2016 
End 10/2020
 
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 Motors
Amount £864,318 (GBP)
Funding ID EP/G037930/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2009 
End 05/2013
 
Description Molecular Software and Hardware for Programmed Chemical Synthesis
Amount £138,284 (GBP)
Funding ID EP/F056605/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 07/2008 
End 07/2011
 
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 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 ROR/ES/AT 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint research, initiated by EPSRC Sandpit, on DNA-programmed chemical synthesis. Oxford contribution: DNA mechanisms for control of autonomous synthesis.
Collaborator Contribution Joint research, initiated by EPSRC Sandpit, on DNA-programmed chemical synthesis. Warwick / Southampton / York contributions: polymer chemistry / synthesis, control theory.
Impact Please see outcomes of grants EP/F008597/1, EP/F056605/1 (also EP/I016651/1, BB/J00054X/1) Interdisciplinary: Physics, Chemistry
Start Year 2007
 
Description ROR/ES/AT 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint research, initiated by EPSRC Sandpit, on DNA-programmed chemical synthesis. Oxford contribution: DNA mechanisms for control of autonomous synthesis.
Collaborator Contribution Joint research, initiated by EPSRC Sandpit, on DNA-programmed chemical synthesis. Warwick / Southampton / York contributions: polymer chemistry / synthesis, control theory.
Impact Please see outcomes of grants EP/F008597/1, EP/F056605/1 (also EP/I016651/1, BB/J00054X/1) Interdisciplinary: Physics, Chemistry
Start Year 2007
 
Description ROR/ES/AT 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint research, initiated by EPSRC Sandpit, on DNA-programmed chemical synthesis. Oxford contribution: DNA mechanisms for control of autonomous synthesis.
Collaborator Contribution Joint research, initiated by EPSRC Sandpit, on DNA-programmed chemical synthesis. Warwick / Southampton / York contributions: polymer chemistry / synthesis, control theory.
Impact Please see outcomes of grants EP/F008597/1, EP/F056605/1 (also EP/I016651/1, BB/J00054X/1) Interdisciplinary: Physics, Chemistry
Start Year 2007