A Digital DNA Nano Writer (DNA NanoFab)
Lead Research Organisation:
University of Glasgow
Department Name: School of Chemistry
Abstract
Today gene sequencing is dropping in price with the $1000 dollar genome a real possibility but what about the direct writing of DNA? Progress in DNA sequencing is down to novel developments in electronic 'read' technology but currently there is no direct 'write'. Indirect methods such as DNA or peptide synthesis are improving but these are 'bulk' methods and sub-unit control on individual molecular strands is not achieved. In this bright idea we will build a hybrid, digital CMOS driven synthetic chemical platform to write DNA directly taking advantage of the speed and parallelism of CMOS aiming for GHz write rates on a single strand of DNA and scale up using PCR. Not only will this allow the 'direct' writing of DNA but also of proteins and polymer chains. This idea is transformative since the end result will be a system that allows the digital control of matter combining digital synthesis and chemical read-write steps. As such, this approach will realise the dream of a molecular assembler allowing access to synthetic DNA an order of magnitude longer in length than the current state of the art, as inexpensively and as quickly as sequence data. In developments beyond DNA, application to polymer science will allow the assembly of digitally defined polymer strands subunit by subunit allowing a nanopore assembler to be used for the world's first true digital matter fabricator or nano-assembler.
Planned Impact
Who will benefit from this research?
The synthetic biology / polymer / coatings, nano-fabrication industries will be the major beneficiaries of this research at all levels from multi-nationals to SMEs and spin out companies. In addition UK HEIs, students and the general public will also be beneficiaries as well as the UK-PLC as a whole.
How will they benefit from this research?
Industry: The synthetic biology / polymer / coatings, nano-fabrication industries will benefit from the new technologies generated in this research since it will provide, new paradigms in nanoassembly, devices and systems for application across a range of sectors with the possibility of delivering breakthroughs that could result in disruptive technologies (e.g. synthetic biology that allows DNA writing at the Ghz). The interactions between Chemists, Polymer scientists, synthetic biologists, Physicists, Engineers, and Biosciences proposed in this grant will also yield great potential teaching and research benefits for the students and the University. This is because undergraduate, ERASMUS, and PhD students will get the chance to take part in research that crosses the interface of this project and it may also be possible to develop a research masters based on this area that will train the next generation of researchers and engineers. General Public: The general public will benefit from this research from the increase in wealth that will be developed and the public understanding and promotion of science activities planned through public lectures at Glasgow / Edinburgh Science Weeks, Café Scientifique. e.g. The PI gave a TED talk on 'inorganic biology' which was watched by over 160,000 in just one week after release on the web.
The synthetic biology / polymer / coatings, nano-fabrication industries will be the major beneficiaries of this research at all levels from multi-nationals to SMEs and spin out companies. In addition UK HEIs, students and the general public will also be beneficiaries as well as the UK-PLC as a whole.
How will they benefit from this research?
Industry: The synthetic biology / polymer / coatings, nano-fabrication industries will benefit from the new technologies generated in this research since it will provide, new paradigms in nanoassembly, devices and systems for application across a range of sectors with the possibility of delivering breakthroughs that could result in disruptive technologies (e.g. synthetic biology that allows DNA writing at the Ghz). The interactions between Chemists, Polymer scientists, synthetic biologists, Physicists, Engineers, and Biosciences proposed in this grant will also yield great potential teaching and research benefits for the students and the University. This is because undergraduate, ERASMUS, and PhD students will get the chance to take part in research that crosses the interface of this project and it may also be possible to develop a research masters based on this area that will train the next generation of researchers and engineers. General Public: The general public will benefit from this research from the increase in wealth that will be developed and the public understanding and promotion of science activities planned through public lectures at Glasgow / Edinburgh Science Weeks, Café Scientifique. e.g. The PI gave a TED talk on 'inorganic biology' which was watched by over 160,000 in just one week after release on the web.
Organisations
People |
ORCID iD |
Leroy Cronin (Principal Investigator) |
Publications
Anamimoghadam O
(2015)
Electronically Stabilized Nonplanar Phenalenyl Radical and Its Planar Isomer.
in Journal of the American Chemical Society
Cameron JM
(2016)
Investigating the Transformations of Polyoxoanions Using Mass Spectrometry and Molecular Dynamics.
in Journal of the American Chemical Society
Caramelli D
(2018)
Networking chemical robots for reaction multitasking.
in Nature communications
Caramelli D
(2021)
Discovering New Chemistry with an Autonomous Robotic Platform Driven by a Reactivity-Seeking Neural Network.
in ACS central science
Chen J
(2017)
Design and Performance of Rechargeable Sodium Ion Batteries, and Symmetrical Li-Ion Batteries with Supercapacitor-Like Power Density Based upon Polyoxovanadates
in Advanced Energy Materials
Colón-Santos S
(2019)
Taming the Combinatorial Explosion of the Formose Reaction via Recursion within Mineral Environments
in ChemSystemsChem
Colón-Santos S
(2019)
Taming the Combinatorial Explosion of the Formose Reaction via Recursion within Mineral Environments
in ChemSystemsChem
Doran D
(2019)
Emergence of Function and Selection from Recursively Programmed Polymerisation Reactions in Mineral Environments.
in Angewandte Chemie (International ed. in English)
Dragone V
(2017)
An autonomous organic reaction search engine for chemical reactivity.
in Nature communications
Duros V
(2017)
Human versus Robots in the Discovery and Crystallization of Gigantic Polyoxometalates
in Angewandte Chemie
Duros V
(2019)
Intuition-Enabled Machine Learning Beats the Competition When Joint Human-Robot Teams Perform Inorganic Chemical Experiments.
in Journal of chemical information and modeling
Duros V
(2017)
Human versus Robots in the Discovery and Crystallization of Gigantic Polyoxometalates.
in Angewandte Chemie (International ed. in English)
Granda JM
(2018)
Controlling an organic synthesis robot with machine learning to search for new reactivity.
in Nature
Grizou J
(2020)
A curious formulation robot enables the discovery of a novel protocell behavior.
in Science advances
Gromski P
(2019)
How to explore chemical space using algorithms and automation
in Nature Reviews Chemistry
Gromski P
(2020)
Universal Chemical Synthesis and Discovery with 'The Chemputer'
in Trends in Chemistry
Kitson PJ
(2016)
The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot.
in Beilstein journal of organic chemistry
Kitson PJ
(2018)
Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals.
in Science (New York, N.Y.)
Lin CG
(2018)
Digital Control of Multistep Hydrothermal Synthesis by Using 3D Printed Reactionware for the Synthesis of Metal-Organic Frameworks.
in Angewandte Chemie (International ed. in English)
Martin-Sabi M
(2018)
Redox tuning the Weakley-type polyoxometalate archetype for the oxygen evolution reaction.
in Nature catalysis
Minato T
(2021)
Robotic Stepwise Synthesis of Hetero-Multinuclear Metal Oxo Clusters as Single-Molecule Magnets.
in Journal of the American Chemical Society
Miras HN
(2020)
Spontaneous formation of autocatalytic sets with self-replicating inorganic metal oxide clusters.
in Proceedings of the National Academy of Sciences of the United States of America
Parrilla-Gutierrez JM
(2020)
A programmable chemical computer with memory and pattern recognition.
in Nature communications
Parrilla-Gutierrez JM
(2017)
Adaptive artificial evolution of droplet protocells in a 3D-printed fluidic chemorobotic platform with configurable environments.
in Nature communications
Points LJ
(2018)
Artificial intelligence exploration of unstable protocells leads to predictable properties and discovery of collective behavior.
in Proceedings of the National Academy of Sciences of the United States of America
Salley D
(2020)
A nanomaterials discovery robot for the Darwinian evolution of shape programmable gold nanoparticles.
in Nature communications
Salley DS
(2020)
A Modular Programmable Inorganic Cluster Discovery Robot for the Discovery and Synthesis of Polyoxometalates.
in ACS central science
Sans V
(2016)
Towards dial-a-molecule by integrating continuous flow, analytics and self-optimisation.
in Chemical Society reviews
Steiner S
(2019)
Organic synthesis in a modular robotic system driven by a chemical programming language.
in Science (New York, N.Y.)
Surman AJ
(2019)
Environmental control programs the emergence of distinct functional ensembles from unconstrained chemical reactions.
in Proceedings of the National Academy of Sciences of the United States of America
Suárez-Marina I
(2019)
Integrated synthesis of nucleotide and nucleosides influenced by amino acids
in Communications Chemistry
Suárez-Marina I
(2018)
Integrated Synthesis of Nucleotide and Nucleosides Directed by Amino Acids
Szymanski JK
(2018)
Exploring Strategies To Bias Sequence in Natural and Synthetic Oligomers and Polymers.
in Accounts of chemical research
Taylor JW
(2017)
Autonomous model protocell division driven by molecular replication.
in Nature communications
Tsuda S
(2015)
Customizable 3D Printed 'Plug and Play' Millifluidic Devices for Programmable Fluidics.
in PloS one
Turk-MacLeod R
(2018)
Approach to classify, separate, and enrich objects in groups using ensemble sorting.
in Proceedings of the National Academy of Sciences of the United States of America
Vilà-Nadal L
(2017)
Design and synthesis of polyoxometalate-framework materials from cluster precursors
in Nature Reviews Materials
Ye JC
(2018)
Strategies to Explore and Develop Reversible Redox Reactions of Li-S in Electrode Architectures Using Silver-Polyoxometalate Clusters.
in Journal of the American Chemical Society
Yoshida M
(2017)
Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro.
in Nature communications
Zalesskiy SS
(2019)
3D designed and printed chemical generators for on demand reagent synthesis.
in Nature communications
Zheng Q
(2018)
Self-Sorting of Heteroanions in the Assembly of Cross-Shaped Polyoxometalate Clusters
in Journal of the American Chemical Society
Title | Brainwaves |
Description | Prof Cronin has appeared on the BBC Radio Scotland "Brainwaves" program, in which he discusses his work, the origin of life, and his development as a scientist. (link below for a limited time only) |
Type Of Art | Film/Video/Animation |
Year Produced | 2016 |
Impact | Scottish audience (but also available on-line) |
URL | http://www.bbc.co.uk/programmes/b070d3yb |
Title | Disruptive Interview |
Description | In an interview for the 3D printing magazine "Disruptive", Lee Cronin discusses his approach of using 3D printing technology for drug discovery and pharmaceuticals, and the digitalisation of the chemical world. |
Type Of Art | Film/Video/Animation |
Year Produced | 2015 |
Impact | target audience |
URL | http://www.disruptivemagazine.com/opinion/disruptive-interview-lee-cronin-regius-chair-chemistry-uni... |
Title | People Behind the Science |
Description | Prof Cronin has appeared on the "People Behind the Science" podcast, where he shared his views on the Origin of Life, and on how chemistry gets complicated, as well as discussing his life as a scientist. |
Type Of Art | Film/Video/Animation |
Year Produced | 2015 |
Impact | inspiration |
URL | http://www.peoplebehindthescience.com/dr-lee-cronin/ |
Title | TED Talk |
Description | The idea is to make a device that could download plans for molecules and create them, in exactly the way that 3D printers can download plans and create objects. He would have a universal set of software, hardware and inks, and he believes all of them, including the ink, could be fantastically cheap. The software would be the product; the materials would be commodities. |
Type Of Art | Film/Video/Animation |
Year Produced | 2012 |
Impact | What would this mean? It would mean that you could print your own medicine. First, his team going to look at drug discovery and manufacturing. If drugs could be manufactured easily, they could be distributed anywhere - even printed at the point of need. If a new super-bug emerges, you could print a treatment right where it breaks out. Ultimately, Cronin says, "For me the cool bit, going into the future, is the idea of taking your own stem cells with your own genes and environment and printing your own medicine." Quickly delivered, cheap, personalized medicine. Does that sound like enough? If not, in the long long run, "You could make a matter fabricator. Beam me up, Scotty!" |
URL | http://blog.ted.com/lee-cronin-at-tedglobal2012/ |
Title | Through the Wormhole |
Description | Lee Cronin and Cronin group research were featured on the latest episode of Through the Wormhole. Lee explained his theory of chemical evolution that pre-dates biological evolution without genes. The episode was broadcast on the Science Channel, and the Cronin Group research can be seen in the first section of the 1-hour episode. (with Morgan Freeman) |
Type Of Art | Film/Video/Animation |
Year Produced | 2015 |
Impact | Large audience. |
URL | http://www.dailymotion.com/video/x2qd2qu |
Description | We discovered that the ability to react DNA base pairs in electric fields was not possible since polymerisation reactions could not be controlled. Given the nature of the funding was for risky big ideas we really embraced this and developed new approaches to explore how sequence based polymerisations could be controlled. In failing to get good control we have : 1) Worked out how to sequence ensembles of polymer sequences covering a large amount of chemical space 2) Developed new electrode arrays for controlling synthesis and modulating reactivity. 3) Developed new sequencing methods using machine learning on mass spectrometry data. More recently we have developed a universal automated peptide synthesiser module for the Chemputer which allows combination of peptide synthesis and further organic chemistry in one system. This may provide a route to digital DNA synthesis with the ability to 'write' by making available much of the entire chemical reactivity literature to perform transformations on individual base pairs. |
Exploitation Route | This work will be very important for the origins of life community in terms of explaining how sequence systems for genetics emerged. Also this work will develop new informatics for exploring sequence space outside of normal biology. |
Sectors | Chemicals Digital/Communication/Information Technologies (including Software) |
Description | We are using the sequencing method to develop a new life detection system for use by NASA and Breakthrough Prize .org. This will be to build a space mission to use mass spec to look for genetic polymers in space and on other planets in the solar system. |
First Year Of Impact | 2018 |
Sector | Aerospace, Defence and Marine,Culture, Heritage, Museums and Collections |
Impact Types | Cultural Societal |
Title | The Chemputer |
Description | A universal modular robotic synthesiser which can undertake ca. 60% of the batch reactions in the chemical literature. This also includes the XDL language and ontology for translating chemical procedures into universally readable actionable code which can potentially be implemented in any robotic system. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | 19 News outlets have reported on this discovery. Plans are underway to setup a spinout and patent aspects of the discovery. https://www.altmetric.com/details/45198487/news https://www.altmetric.com/details/51967737/news |
URL | http://www.chem.gla.ac.uk/cronin/chemify/ |
Title | One dimensional transport in silicon nanowire junction-less field effect transistors |
Description | Important collection of information for future research. |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Easy and quick access to a database of silicon nanowires |