Molecular Software and Hardware for Programmed Chemical Synthesis
Lead Research Organisation:
University of Oxford
Department Name: Oxford Physics
Abstract
We intend to design a nanoscale chemical factory in which the machines, like the products, are molecules. The factory will not only build molecules but will be capable of evolving them to have desirable properties. The products will be linear molecules produced by linking together smaller building blocks in a defined sequence - at each stage the molecular machinery will be capable of choosing the correct building block from a range of possibilities. The system will be capable of synthesizing a library of molecules with different sequences and selecting 'successful' molecules for their fitness to perform a specified task. We will also develop designs for more powerful systems in which the molecular machinery responsible for chemical synthesis has internal computing power and can direct its own operation.
Publications
McKee ML
(2010)
Multistep DNA-templated reactions for the synthesis of functional sequence controlled oligomers.
in Angewandte Chemie (International ed. in English)
McKee ML
(2011)
Peptidomimetic bond formation by DNA-templated acyl transfer.
in Organic & biomolecular chemistry
Muscat RA
(2011)
A programmable molecular robot.
in Nano letters
Santini CC
(2012)
A DNA network as an information processing system.
in International journal of molecular sciences
McKee ML
(2012)
Programmable one-pot multistep organic synthesis using DNA junctions.
in Journal of the American Chemical Society
Milnes PJ
(2012)
Sequence-specific synthesis of macromolecules using DNA-templated chemistry.
in Chemical communications (Cambridge, England)
Costa Santini C
(2013)
A clocked finite state machine built from DNA.
in Chemical communications (Cambridge, England)
Dannenberg F
(2014)
DNA walker circuits: computational potential, design, and verification
in Natural Computing
Meng W
(2016)
An autonomous molecular assembler for programmable chemical synthesis.
in Nature chemistry
| Description | This grant is closely linked to another - 'Software-controlled assembly of oligomers' - and is part of the same collaborative research programme. We intend to create a nanoscale chemical factory in which the machines, like the products, are molecules. The designed products will be linear molecules produced by linking together smaller building blocks in a defined sequence - at each stage the molecular machinery will be capable of choosing the correct building block from a range of possibilities. The system will be capable of synthesizing a library of molecules with different sequences and selecting 'successful' molecules for their fitness to perform a specified task. We have developed systems, based on nanostructures made from DNA, that control the routing of a cargo within a branched track network. Under a linked grant, we have developed methods for controlling sequential chemical reactions using DNA. We have also worked on designs for more powerful systems in which the molecular machinery responsible for chemical synthesis has internal computing power and can direct its own operation. Many of the components for our nanoscale factory are therefore in place: we have DNA-directed chemistry and DNA assembly lines with controlled routing that will enable control of the molecular product formed. This grant also supported closely connected developments in DNA-based computation, intended to underpin future control mechanisms for synthetic molecular machinery used for programmed synthesis. |
| 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 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 |