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.

Publications

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Anamimoghadam O (2015) Electronically Stabilized Nonplanar Phenalenyl Radical and Its Planar Isomer. in Journal of the American Chemical Society

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Caramelli D (2018) Networking chemical robots for reaction multitasking. in Nature communications

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Duros V (2017) Human versus Robots in the Discovery and Crystallization of Gigantic Polyoxometalates. in Angewandte Chemie (International ed. in English)

 
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