14TSB_SynBio Automated Gene Assembly From Codons to Complete Genes and Pathways
Lead Research Organisation:
Imperial College London
Department Name: Life Sciences
Abstract
The ability to assemble genes from smaller DNA fragments or generate combinatorial libraries of genetic mutations is fundamental to the field of synthetic biology. Different methodologies exist for their fabrication but enzymatic assembly produces consistently high quality products compared to other methods which is essential for downstream processes for improved characteristics (whether this is for improved strain phenotype or an improved protein function/yield). The potential to achieve this in a high throughput, automatable fashion would be a powerful and valuable tool for commercialisation in the synthetic biology arena. In this respect, we have previously developed a technology that can create random stretches of gene fragments using enzymatic additions of codon triplets. We now wish to investigate further procedures to assemble diversified gene fragments, in particular antibody variable loops, into whole genes in an automated fashion. Imperial College is automating assembly methods that would be enabling for the project by bridging the scale from codons to genes and pathways, thereby potentially the opening up new market areas.
Technical Summary
The ability to assemble genes from smaller DNA fragments or generate combinatorial libraries of genetic mutations is fundamental to the field of synthetic biology. Different methodologies exist for their fabrication but enzymatic assembly produces consistently high quality products compared to other methods which is essential for downstream processes for improved characteristics (whether this is for improved strain phenotype or an improved protein function/yield). The potential to achieve this in a high throughput, automatable fashion would be a powerful and valuable tool for commercialisation in the synthetic biology arena. In this respect, we have previously developed a technology that can create random stretches of gene fragments using enzymatic additions of codon triplets. We now wish to investigate further procedures to assemble diversified gene fragments, in particular antibody variable loops, into whole genes in an automated fashion. Imperial College is automating assembly methods that would be enabling for the project by bridging the scale from codons to genes and pathways, thereby potentially the opening up new market areas.
Planned Impact
The beneficiaries of this project can be defined as the researchers involved, and both the synthetic biology and academic communities as well as industry.
- Measurable impacts from this will include research output, interactions and presentations by the PI and PDRA at meetings both internally, externally and internationally, as well as the future placement of the PDRA involved.
The broader academic synthetic biology community will stand to benefit from this research.
- Measurable impacts from this research will be the development of new platform approaches that lead to the integration of codon diversification with DNA assembly of larger fragments.
Enzyme engineering is currently an enormous industry that underpins many biotech applications. The emergence of synthetic biology and its ability to more rapidly develop biological systems and new pathways for the production of fine chemicals in a sustainable manner will only increase the demand for new protein functionality and specificity. The technology that we present in this grant has the potential to be a disruptive technology in this space and radically alter the way that people perceive for evolving new functionality and specificity. Its application is not specific to a single domain but can be envisioned equally in antibody engineering for sensors, diagnostics and thereapeutics as well as enzymatic pathways for production of value chemicals.
- Measurable impacts will be implementation of the new platform within Isogenica and an ongoing collaboration between Imperial College and Isogenica.
The ethos of the Synthetic Biology community and CSynBI is to include public dialogue and outreach at every stage of research from tools to applications.
- Measurable impacts will be any future engagement activities undertaken during the lifetime of the grant.
Dissemination of results is a key feature of scientific research and the scientific endeavour.
- Measurable impacts will be publications and presentations during the lifetime of the grant and the following 12 months
- Measurable impacts from this will include research output, interactions and presentations by the PI and PDRA at meetings both internally, externally and internationally, as well as the future placement of the PDRA involved.
The broader academic synthetic biology community will stand to benefit from this research.
- Measurable impacts from this research will be the development of new platform approaches that lead to the integration of codon diversification with DNA assembly of larger fragments.
Enzyme engineering is currently an enormous industry that underpins many biotech applications. The emergence of synthetic biology and its ability to more rapidly develop biological systems and new pathways for the production of fine chemicals in a sustainable manner will only increase the demand for new protein functionality and specificity. The technology that we present in this grant has the potential to be a disruptive technology in this space and radically alter the way that people perceive for evolving new functionality and specificity. Its application is not specific to a single domain but can be envisioned equally in antibody engineering for sensors, diagnostics and thereapeutics as well as enzymatic pathways for production of value chemicals.
- Measurable impacts will be implementation of the new platform within Isogenica and an ongoing collaboration between Imperial College and Isogenica.
The ethos of the Synthetic Biology community and CSynBI is to include public dialogue and outreach at every stage of research from tools to applications.
- Measurable impacts will be any future engagement activities undertaken during the lifetime of the grant.
Dissemination of results is a key feature of scientific research and the scientific endeavour.
- Measurable impacts will be publications and presentations during the lifetime of the grant and the following 12 months
Organisations
People |
ORCID iD |
Geoffrey Baldwin (Principal Investigator) |
Publications
Casini A
(2014)
R2oDNA designer: computational design of biologically neutral synthetic DNA sequences.
in ACS synthetic biology
Casini A
(2015)
Bricks and blueprints: methods and standards for DNA assembly.
in Nature reviews. Molecular cell biology
Storch M
(2015)
BASIC: A New Biopart Assembly Standard for Idempotent Cloning Provides Accurate, Single-Tier DNA Assembly for Synthetic Biology.
in ACS synthetic biology
Storch M
(2017)
BASIC: A Simple and Accurate Modular DNA Assembly Method.
in Methods in molecular biology (Clifton, N.J.)
Description | We have further developed our DNA assembly technology We have also discovered and characterised new DNA ligases that will improve the workflow of our industrial collaborator as well as improving our DNA assembly |
Exploitation Route | We aim to characterise the novel ligases further and commercially exploit them through licensing deals. |
Sectors | Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | Our DNA technology has been used by Industry. We have the possibility of commercial exploitation of our findings |
First Year Of Impact | 2014 |
Sector | Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | A semi-autonomous robot synthetic biologist for industrial biodesign and manufacturing |
Amount | £884,199 (GBP) |
Funding ID | EP/R034915/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2018 |
End | 08/2022 |
Description | BBSRC Network in Biotechnology |
Amount | £99,000 (GBP) |
Funding ID | Sub project from University of Manchester who hold the main Network award |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2015 |
End | 05/2016 |
Description | EPSRC Innovation and Knowledge Centre in Synthetic Biology - 24 month review |
Amount | £2,010,000 (GBP) |
Funding ID | (EP/N023854/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2015 |
End | 11/2018 |
Description | SynbiCITE - Innovation and Knowledge Centre in Synthetic Biology - Collaborative Programme - Tranche 1 |
Amount | £2,907,115 (GBP) |
Funding ID | EP/M006700/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2014 |
End | 09/2017 |
Title | BASIC DNA assembly |
Description | This method provides for a highly scalable and efficient standardised method for assembling DNA parts to create new biological systems. |
Type Of Material | Technology assay or reagent |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | High throughput DNA assembly is currently being implemented on an automated workflow for industrial collaboration. We have collaborations with a number of academic and industrial partners to translate this technology. |
Description | BioSynSys 2015 Biologie de synthese et des systemes |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The establishment of a French GDR for systems and synthetic biology is intended to bring together the collective efforts of the French nation in this area of research as well as providing a method for further international interaction. I was invited as a plenary speaker to their inaugural conference. |
Year(s) Of Engagement Activity | 2015 |
URL | http://biosynsys2015.sciencesconf.org/?lang=en |
Description | Invited Seminar at University of Stuttgart |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited to give a seminar to the Institut für Bioverfahrenstechnik |
Year(s) Of Engagement Activity | 2015 |
Description | Invited seminar at LMU Munich |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited to give a plenary talk at the Institute retreat. |
Year(s) Of Engagement Activity | 2015 |
Description | SynBioBeta London 2015 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | SynBioBeta is a conference that acts as a hub at the academic and business interface of synthetic biology. The fast moving and adaptive field makes for a highly dynamic environment with the engagement of many SMEs and startups |
Year(s) Of Engagement Activity | 2015 |
URL | http://synbiobeta.com/conferences/synbiobeta-london-2015/ |