Evolution of Novel Biopolymers
Lead Research Organisation:
MRC Laboratory of Molecular Biology
Abstract
Every organism’s blueprint is stored as genetic information encoded in DNA. Before a cell can divide, its genetic information needs to be copied and duplicated. This process is carried out by sophisticated enzymes called polymerases. The astonishing ability of polymerases to both “read” and “write” genetic information is vital to all life on earth and central to modern biology and medicine enabling genome sequencing and the polymerase chain reaction. Our work is aimed at the engineering of novel polymerases capable of activity in unfavourable conditions, and utilising unnatural building blocks. Such "designer" polymerases will be key enabling technologies for the generation of next-generation nucleic acid drugs, sensors and nanomaterials.
Technical Summary
Synthetic biology seeks to probe fundamental aspects of biological form and function by construction (i.e. resynthesis) rather than deconstruction (analysis). Synthesis thus complements reductionist and analytic studies of life, and allows novel approaches towards fundamental biological questions.
We have been exploiting the synthesis paradigm to explore the chemical etiology of the genetic apparatus shared by all life on earth. Specifically, we ask why information storage and propagation in biological systems is based on just two types of nucleic acids, DNA and RNA. Is the chemistry of life’s genetic system based on chance or necessity? Does it reflect a "frozen accident", imposed at the origin of life, or are DNA and RNA functionally superior to simple alternatives.
We have developed advanced generation selection strategies, that allow the evolution of polymerases capable of utilizing exclusively unnatural nucleotide substrates enabling the enzymatic synthesis, replication and evolution of entirely synthetic genetic polymers (XNA). Such systems expand the central dogma and will conclusively address questions such as the capacity of genetic polymers other than DNA and RNA for information storage and propagation (i.e. heredity). Beyond heredity, we have demonstrated a capacity for Darwinian evolution by the de novo selection of specific ligands (XNA aptamers) and catalysts (XNAzymes) based on these entirely synthetic backbones. Thus, key hallmarks of living systems, including heredity and evolution are not limited to DNA and RNA but can be implemented in synthetic polymers and are likely to be emergent properties of polymers capable of information storage.
The further exploration of the informational, structural and catalytic potential of synthetic genetic polymers, should advance our understanding of the parameters of chemical information encoding, and will provide a source of novel ligands, catalysts and nanostructures with tailor-made chemistries for applications in biotechnology and medicine.
We have also leveraged our selection technology to make progress in the engineering and evolution of RNA polymerase ribozymes towards a general polymerase and self-replication capacity We have discovered RNA polymerase ribozymes that are capable of the templated synthesis (i.e. transcription) of another simple ribozyme or RNA oligomers exceeding their own size (>200 nts), a key milestone on the road to self-replication.
We have been exploiting the synthesis paradigm to explore the chemical etiology of the genetic apparatus shared by all life on earth. Specifically, we ask why information storage and propagation in biological systems is based on just two types of nucleic acids, DNA and RNA. Is the chemistry of life’s genetic system based on chance or necessity? Does it reflect a "frozen accident", imposed at the origin of life, or are DNA and RNA functionally superior to simple alternatives.
We have developed advanced generation selection strategies, that allow the evolution of polymerases capable of utilizing exclusively unnatural nucleotide substrates enabling the enzymatic synthesis, replication and evolution of entirely synthetic genetic polymers (XNA). Such systems expand the central dogma and will conclusively address questions such as the capacity of genetic polymers other than DNA and RNA for information storage and propagation (i.e. heredity). Beyond heredity, we have demonstrated a capacity for Darwinian evolution by the de novo selection of specific ligands (XNA aptamers) and catalysts (XNAzymes) based on these entirely synthetic backbones. Thus, key hallmarks of living systems, including heredity and evolution are not limited to DNA and RNA but can be implemented in synthetic polymers and are likely to be emergent properties of polymers capable of information storage.
The further exploration of the informational, structural and catalytic potential of synthetic genetic polymers, should advance our understanding of the parameters of chemical information encoding, and will provide a source of novel ligands, catalysts and nanostructures with tailor-made chemistries for applications in biotechnology and medicine.
We have also leveraged our selection technology to make progress in the engineering and evolution of RNA polymerase ribozymes towards a general polymerase and self-replication capacity We have discovered RNA polymerase ribozymes that are capable of the templated synthesis (i.e. transcription) of another simple ribozyme or RNA oligomers exceeding their own size (>200 nts), a key milestone on the road to self-replication.
Organisations
- MRC Laboratory of Molecular Biology, United Kingdom (Lead Research Organisation)
- University of Edinburgh, United Kingdom (Collaboration)
- Solexa (Collaboration)
- University of Leuven (Collaboration)
- Human Genetic Signatures (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- Agilent Technologies UK Ltd (Collaboration)
- University of Bonn, Germany (Collaboration)
- New England Biolabs (Collaboration)
- Life Technologies (Collaboration)
- University of Cambridge, United Kingdom (Collaboration)
- Domantis Ltd, United Kingdom (Collaboration)
- Arizona State University (Collaboration)
- Medical Research Council (Collaboration)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (Collaboration)
- University of Konstanz (Collaboration)
- AstraZeneca plc (Collaboration)
- University of Southern Denmark, Denmark (Collaboration)
- Swiss Federal Institute of Technology (ETH), Zurich (Collaboration)
- Stanford University, United States (Collaboration)
- University of Notre Dame (Collaboration)
- Exiqon, Denmark (Collaboration)
- RIKEN, Japan (Collaboration)
- Helicos Biosciences (Collaboration)
People |
ORCID iD |
| Philipp Holliger (Principal Investigator) |
Publications
Alves Ferreira-Bravo I
(2015)
Selection of 2'-deoxy-2'-fluoroarabinonucleotide (FANA) aptamers that bind HIV-1 reverse transcriptase with picomolar affinity.
in Nucleic acids research
Arangundy-Franklin S
(2019)
A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids.
in Nature chemistry
Attwater J
(2012)
Origins of life: The cooperative gene.
in Nature
Attwater J
(2014)
A synthetic approach to abiogenesis.
in Nature methods
Attwater J
(2018)
Ribozyme-catalysed RNA synthesis using triplet building blocks.
in eLife
Attwater J
(2013)
Chemical fidelity of an RNA polymerase ribozyme
in Chemical Science
Attwater J
(2010)
Ice as a protocellular medium for RNA replication.
in Nature communications
Attwater J
(2013)
In-ice evolution of RNA polymerase ribozyme activity.
in Nature chemistry
Baar C
(2011)
Molecular breeding of polymerases for resistance to environmental inhibitors.
in Nucleic acids research
Bande O
(2015)
Isoguanine and 5-methyl-isocytosine bases, in vitro and in vivo.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Burnett DL
(2018)
Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination.
in Science (New York, N.Y.)
Compte M
(2007)
Inhibition of tumor growth in vivo by in situ secretion of bispecific anti-CEA x anti-CD3 diabodies from lentivirally transduced human lymphocytes.
in Cancer gene therapy
Cozens C
(2015)
Enzymatic Synthesis of Nucleic Acids with Defined Regioisomeric 2'-5' Linkages.
in Angewandte Chemie (International ed. in English)
Cozens C
(2012)
A short adaptive path from DNA to RNA polymerases.
in Proceedings of the National Academy of Sciences of the United States of America
D'Abbadie M
(2007)
Molecular breeding of polymerases for amplification of ancient DNA.
in Nature biotechnology
Gallego J
(2007)
Solution structure and dynamics of DNA duplexes containing the universal base analogues 5-nitroindole and 5-nitroindole 3-carboxamide.
in Nucleic acids research
Ghadessy FJ
(2007)
Compartmentalized self-replication: a novel method for the directed evolution of polymerases and other enzymes.
in Methods in molecular biology (Clifton, N.J.)
Graci JD
(2007)
Lethal mutagenesis of poliovirus mediated by a mutagenic pyrimidine analogue.
in Journal of virology
Graci JD
(2008)
Lethal mutagenesis of picornaviruses with N-6-modified purine nucleoside analogues.
in Antimicrobial agents and chemotherapy
He C
(2017)
A viscous solvent enables information transfer from gene-length nucleic acids in a model prebiotic replication cycle.
in Nature chemistry
Holliger P
(2009)
Systems Biology and Synthetic Biology
Houlihan G
(2017)
Exploring the Chemistry of Genetic Information Storage and Propagation through Polymerase Engineering.
in Accounts of chemical research
Houlihan G
(2017)
Engineering and application of polymerases for synthetic genetics.
in Current opinion in biotechnology
Jaeger KE
(2010)
Chemical biotechnology--a marriage of convenience and necessity.
in Current opinion in biotechnology
Loakes D
(2009)
Evolving a polymerase for hydrophobic base analogues.
in Journal of the American Chemical Society
Loakes D
(2009)
Darwinian chemistry: towards the synthesis of a simple cell.
in Molecular bioSystems
Loakes D
(2009)
Polymerase engineering: towards the encoded synthesis of unnatural biopolymers.
in Chemical communications (Cambridge, England)
Luzi S
(2015)
Subunit disassembly and inhibition of TNFa by a semi-synthetic bicyclic peptide.
in Protein engineering, design & selection : PEDS
Millar D
(2015)
A polymerase engineered for bisulfite sequencing.
in Nucleic acids research
Mutschler H
(2015)
Freeze-thaw cycles as drivers of complex ribozyme assembly.
in Nature chemistry
Mutschler H
(2018)
Random-sequence genetic oligomer pools display an innate potential for ligation and recombination.
in eLife
Mutschler H
(2014)
Non-canonical 3'-5' extension of RNA with prebiotically plausible ribonucleoside 2',3'-cyclic phosphates.
in Journal of the American Chemical Society
Ong JL
(2006)
Directed evolution of DNA polymerase, RNA polymerase and reverse transcriptase activity in a single polypeptide.
in Journal of molecular biology
Pinheiro VB
(2013)
Synthetic polymers and their potential as genetic materials.
in BioEssays : news and reviews in molecular, cellular and developmental biology
Pinheiro VB
(2012)
The XNA world: progress towards replication and evolution of synthetic genetic polymers.
in Current opinion in chemical biology
Pinheiro VB
(2014)
Compartmentalized Self-Tagging for In Vitro-Directed Evolution of XNA Polymerases.
in Current protocols in nucleic acid chemistry
Pinheiro VB
(2014)
Towards XNA nanotechnology: new materials from synthetic genetic polymers.
in Trends in biotechnology
Pinheiro VB
(2012)
Synthetic genetic polymers capable of heredity and evolution.
in Science (New York, N.Y.)
Pinheiro, V.B.
(2012)
Protein Engineering Handbook: Volume 3
Ramsay N
(2010)
CyDNA: synthesis and replication of highly Cy-dye substituted DNA by an evolved polymerase.
in Journal of the American Chemical Society
Rose KM
(2019)
Selection of 2'-Deoxy-2'-Fluoroarabino Nucleic Acid (FANA) Aptamers That Bind HIV-1 Integrase with Picomolar Affinity.
in ACS chemical biology
Smith DA
(2012)
Reversible fluorescence photoswitching in DNA.
in The journal of physical chemistry. B
Stadler LK
(2014)
The use of a neutral peptide aptamer scaffold to anchor BH3 peptides constitutes a viable approach to studying their function.
in Cell death & disease
Suzuki T
(2006)
Template properties of mutagenic cytosine analogues in reverse transcription.
in Nucleic acids research
Tagami S
(2017)
Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function.
in Nature chemistry
Taira K
(2008)
Binding of MutS protein to oligonucleotides containing a methylated or an ethylated guanine residue, and correlation with mutation frequency.
in Mutation research
Taylor AI
(2015)
Catalysts from synthetic genetic polymers.
in Nature
Taylor AI
(2019)
Beyond DNA and RNA: The Expanding Toolbox of Synthetic Genetics.
in Cold Spring Harbor perspectives in biology
Taylor AI
(2018)
Selecting Fully-Modified XNA Aptamers Using Synthetic Genetics.
in Current protocols in chemical biology
Taylor AI
(2016)
Nanostructures from Synthetic Genetic Polymers.
in Chembiochem : a European journal of chemical biology
| Description | Royal Society Policy seminar on "Synthetic Biology" |
| Geographic Reach | National |
| Policy Influence Type | Participation in a advisory committee |
| Description | Royal Society of Chemistry Replicating and Learning from Nature Exploration Workshop |
| Geographic Reach | National |
| Policy Influence Type | Participation in a advisory committee |
| Description | 14-ERASynBio INTENSIFYBBSRC |
| Amount | £287,638 (GBP) |
| Funding ID | BB/M005623/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2014 |
| End | 07/2017 |
| Description | Carlsberg Foundation |
| Amount | £50,000 (GBP) |
| Organisation | Carlsberg Foundation |
| Sector | Charity/Non Profit |
| Country | Denmark |
| Start | 10/2018 |
| End | 09/2019 |
| Description | Carlsberg Foundation Internationalisation Fellowship (Kristofferson |
| Amount | kr 425,000 (DKK) |
| Funding ID | CF19-0019 |
| Organisation | Carlsberg Foundation |
| Sector | Charity/Non Profit |
| Country | Denmark |
| Start | 10/2019 |
| End | 09/2020 |
| Description | DFG Fellowship (Baar) |
| Amount | £48,000 (GBP) |
| Organisation | German Research Foundation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | 01/2007 |
| End | 12/2008 |
| Description | DFG, Fellowship |
| Amount | £37,805 (GBP) |
| Organisation | German Research Foundation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | 11/2004 |
| End | 01/2006 |
| Description | EC - Marie Curie Fellowship (Gallego) DNA-origami frame platform for co-evolution ligand selection |
| Amount | € 212,934 (EUR) |
| Funding ID | H2020-MSCA-IF-2018-845303 |
| Organisation | Marie Sklodowska-Curie Actions |
| Sector | Charity/Non Profit |
| Country | Global |
| Start | 04/2019 |
| End | 03/2021 |
| Description | ERASynBio2 - Orthogonal biosystems based on phosphonate XNAs |
| Amount | £250,283 (GBP) |
| Funding ID | UCL Ref 168510 BB/N01023X/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2016 |
| End | 04/2019 |
| Description | EuroSynBio - SYNAPTA |
| Amount | £334,000 (GBP) |
| Funding ID | BB/I004793/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2010 |
| End | 04/2013 |
| Description | FEBS Fellowship |
| Amount | £78,000 (GBP) |
| Organisation | Federation of European Biochemical Societies (FEBS) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2012 |
| End | 06/2015 |
| Description | FP6 NEST Pathfinder |
| Amount | £403,381 (GBP) |
| Organisation | Sixth Framework Programme (FP6) |
| Sector | Public |
| Country | European Union (EU) |
| Start | 05/2006 |
| End | 07/2009 |
| Description | HFSP Fellowship |
| Amount | £93,780 (GBP) |
| Funding ID | LT000045/2012 |
| Organisation | Human Frontier Science Program (HFSP) |
| Sector | Charity/Non Profit |
| Country | France |
| Start | 01/2013 |
| End | 12/2015 |
| Description | Herchel Smith Studentship Christopher Wan |
| Amount | £180,000 (GBP) |
| Organisation | University of Cambridge |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2017 |
| End | 09/2021 |
| Description | Junior Research Fellowship |
| Amount | £55,000 (GBP) |
| Organisation | University of Cambridge |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2011 |
| End | 09/2014 |
| Description | MRC/AZ CRISPR-X: Leveraging XNA technology for advanced genome editing |
| Amount | £206,423 (GBP) |
| Funding ID | BSF35 |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 05/2019 |
| End | 04/2020 |
| Description | MRC/AZ Deep screening: Leveraging NextGen sequencing technology for a quantum leap in ligand discovery |
| Amount | £263,000 (GBP) |
| Funding ID | BSF24 |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 04/2017 |
| End | 03/2019 |
| Description | MRC/AZ Explore XNA Aptamer technology for in vivo selection of targeting moieties and oligonucleotide delivery |
| Amount | £215,642 (GBP) |
| Funding ID | BSF01 |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 06/2015 |
| End | 06/2019 |
| Description | MRC/AZ In Cellulo target discovery using XNA technology |
| Amount | £305,948 (GBP) |
| Funding ID | BSF11 |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 01/2016 |
| End | 01/2019 |
| Description | MRCT DGF Project Grant |
| Amount | £110,000 (GBP) |
| Funding ID | A853-0137 |
| Organisation | MRC-Technology |
| Sector | Private |
| Country | United Kingdom |
| Start | 09/2011 |
| End | 09/2014 |
| Description | NSERC Canada fellowship |
| Amount | £40,000 (GBP) |
| Organisation | Natural Sciences and Engineering Research Council of Canada (NSERC) |
| Sector | Public |
| Country | Canada |
| Start | 10/2007 |
| End | 12/2008 |
| Description | Simons Collaboration on the Origins of Life Postdoctoral Fellowship |
| Amount | $243,000 (USD) |
| Funding ID | 293387 |
| Organisation | Simons Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 11/2013 |
| End | 10/2016 |
| Description | US Gates - Duffy |
| Amount | £44,700 (GBP) |
| Organisation | Higher Education Funding Council for England |
| Department | Gates Cambridge Scholarship |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2016 |
| End | 09/2019 |
| Description | VolkswagenStiftung |
| Amount | € 396,000 (EUR) |
| Organisation | Volkswagen Foundation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | |
| Description | Wellcome Trust Internship |
| Amount | £1,360 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2006 |
| End | 08/2006 |
| Title | CSR |
| Description | polymerases with expanded substrate spectrum |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2008 |
| Provided To Others? | Yes |
| Impact | licensing deals with New England Biolabs, Human Genetic Signatures |
| Title | CST |
| Description | novel polymerases capable of utilizing entirely unnatural orthogonal substrates |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2010 |
| Provided To Others? | Yes |
| Impact | improved tools for e.g. generation of nucleic acid therapeutics |
| Description | CryoEM imaging of XNA nanotechnology objects |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Laboratory of Molecular Biology (LMB) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | first structures of XNA nano-object |
| Description | CyDNA in super-resolution microscopy |
| Organisation | University of Edinburgh |
| Department | School of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | publication: 22861666 (August, 2012) Reversible Fluorescence Photoswitching in DNA. |
| Description | DNA/XNA origami nanopores |
| Organisation | University of Cambridge |
| Department | Department of Biochemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | Deep Screening |
| Organisation | ETH Zurich |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | Hydrophobic base analogues |
| Organisation | Stanford University |
| Department | Department of Chemistry |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | In vivo target discovery |
| Organisation | AstraZeneca |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | LNA and UNA triphosphates as polymerase substrates |
| Organisation | University of Southern Denmark |
| Country | Denmark |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | Mutant Polymerases |
| Organisation | Agilent Technologies |
| Country | United States |
| Sector | Private |
| PI Contribution | generation of novel polymerases with potential biotechnological impact |
| Collaborator Contribution | non-exclusive license for both polymerases and CSR selection technology potential for collaboration |
| Impact | generation of licensing revenue for MRC |
| Description | Mutant Polymerases |
| Organisation | Exiqon |
| Country | Denmark |
| Sector | Private |
| PI Contribution | generation of novel polymerases with potential biotechnological impact |
| Collaborator Contribution | non-exclusive license for both polymerases and CSR selection technology potential for collaboration |
| Impact | generation of licensing revenue for MRC |
| Description | Mutant Polymerases |
| Organisation | Helicos Biosciences |
| Country | United States |
| Sector | Private |
| PI Contribution | generation of novel polymerases with potential biotechnological impact |
| Collaborator Contribution | non-exclusive license for both polymerases and CSR selection technology potential for collaboration |
| Impact | generation of licensing revenue for MRC |
| Description | Mutant Polymerases |
| Organisation | Life Technologies |
| Department | Applied Biosystems |
| Country | United States |
| Sector | Private |
| PI Contribution | generation of novel polymerases with potential biotechnological impact |
| Collaborator Contribution | non-exclusive license for both polymerases and CSR selection technology potential for collaboration |
| Impact | generation of licensing revenue for MRC |
| Description | Mutant Polymerases |
| Organisation | Life Technologies |
| Department | Invitrogen |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | generation of novel polymerases with potential biotechnological impact |
| Collaborator Contribution | non-exclusive license for both polymerases and CSR selection technology potential for collaboration |
| Impact | generation of licensing revenue for MRC |
| Description | Mutant Polymerases |
| Organisation | New England Biolabs |
| Country | United States |
| Sector | Private |
| PI Contribution | generation of novel polymerases with potential biotechnological impact |
| Collaborator Contribution | non-exclusive license for both polymerases and CSR selection technology potential for collaboration |
| Impact | generation of licensing revenue for MRC |
| Description | Mutant Polymerases |
| Organisation | Solexa |
| Country | United States |
| Sector | Private |
| PI Contribution | generation of novel polymerases with potential biotechnological impact |
| Collaborator Contribution | non-exclusive license for both polymerases and CSR selection technology potential for collaboration |
| Impact | generation of licensing revenue for MRC |
| Description | Oligonucleotide arrays |
| Organisation | Agilent Technologies |
| Country | United States |
| Sector | Private |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | Phage Display |
| Organisation | GlaxoSmithKline (GSK) |
| Country | Global |
| Sector | Private |
| PI Contribution | consulting for GSK/ Domantis dispute with AbLynx |
| Collaborator Contribution | GSK/ Domantis dispute with AbLynx |
| Impact | contribution to settlement |
| Start Year | 2008 |
| Description | Polymerase Evolution |
| Organisation | Domantis Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | development of novel directed evolution methodologies for proteins and in particular polymerases |
| Collaborator Contribution | Collaboration agreement with Domantis funded 2 postdoctoral scientists in my group |
| Impact | funding of postdoctoral researchers, cost of patent prosecution, consumables; Collaboration agreement with Domantis funded 2 postdoctoral scientists in my group |
| Description | Polymerases for Bisulfite Sequencing |
| Organisation | Human Genetic Signatures |
| Country | Australia |
| Sector | Private |
| PI Contribution | evaluation agreement |
| Collaborator Contribution | evaluation agreement |
| Impact | evaluation agreement |
| Start Year | 2008 |
| Description | SHAPE mapping of XNAs and RNAs |
| Organisation | University of Notre Dame |
| Department | Department of Chemistry and Biochemistry |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | publication: 25470036 (February, 2015) Catalysts from synthetic genetic polymers. |
| Description | Structural studies of XNA polymerases. |
| Organisation | University of Konstanz |
| Department | Department of Chemistry |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | 23940661 (, 2013) Structures of an apo and a binary complex of an evolved archeal B family DN... |
| Description | TNA triphosphates as polymerase substrates. |
| Organisation | Arizona State University |
| Department | School of Molecular Sciences |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | Translesion synthesis of XNA polymerases |
| Organisation | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | Unnatural base-pair replication in RNA. |
| Organisation | RIKEN |
| Department | RIKEN centre for life science technologies |
| Country | Japan |
| Sector | Public |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | X-ray crystallography of mutant DNA polymerases. |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Laboratory of Molecular Biology (LMB) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | XNA nucleotide and solid-phase synthesis. |
| Organisation | University of Leuven |
| Department | Rega Institute for Medical Research |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Description | XNA side-chain modification chemistry |
| Organisation | University of Bonn |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Scientific |
| Collaborator Contribution | Scientific |
| Impact | N/A |
| Title | Arabino-DNA polymerase |
| Description | polymerase for the synthesis of synthetic genetic polymers based on arabino-nucleotides |
| IP Reference | WO2013156786 |
| Protection | Patent application published |
| Year Protection Granted | 2013 |
| Licensed | No |
| Impact | none |
| Title | Artificial genetic systems |
| Description | An artificial genetic system based on polymerase engineering enabling the discovery of novel biopolymer therapeutics |
| IP Reference | WO2011135280 |
| Protection | Patent application published |
| Year Protection Granted | 2011 |
| Licensed | No |
| Impact | NA |
| Title | CST Emulsions |
| Description | A novel method for the selection of nucleic acid processing and other enzymes and in particular polymerases |
| IP Reference | WO2005045072 |
| Protection | Patent granted |
| Year Protection Granted | |
| Licensed | Yes |
| Impact | A novel method for the selection of nucleic acid processing and other enzymes based on the compartmentalized self-tagging technique |
| Title | CST2.0 |
| Description | improved methodology for CST emulsions, filed as a continuation in part |
| IP Reference | US20100184071 |
| Protection | Patent granted |
| Year Protection Granted | 2010 |
| Licensed | No |
| Impact | Significant improvement on CST (compartmentalised self tagging) method which is already patented and relates to screening of polymerases with specific properties. The method allows for selection of only true positives which was frequently not the case with the original CST. |
| Title | Directed Evolution Method |
| Description | directed evolution method based on the novel principle of compartmentalized self-replication |
| IP Reference | WO2002022869 |
| Protection | Patent granted |
| Year Protection Granted | 2007 |
| Licensed | Yes |
| Impact | Method to select for proteins with altered characteristics. The protein of interest is randomly mutated and variants of it undergo selection based on presence or absence of nucleic acid polymerase activity. |
| Title | E10 polymerase |
| Description | A polymerase for the high-density incorporation of fluorescent-dye labeled nucleotides into DNA |
| IP Reference | US2010035767 |
| Protection | Patent granted |
| Year Protection Granted | 2010 |
| Licensed | Yes |
| Impact | improved microarray protocols, novel diagnostics |
| Title | Emulsion Compositions |
| Description | novel inert oxidant-free emulsion formulation |
| IP Reference | US2008187968 |
| Protection | Patent granted |
| Year Protection Granted | 2008 |
| Licensed | Yes |
| Impact | Invention describes improved chemical composition of two phase emulsions. Such emulsions are of use for large scale screening |
| Title | Hu1 polymerase |
| Description | polymerases with a resitance to common environmental inhibitors e.g. humic acid |
| IP Reference | US2009305345 |
| Protection | Patent granted |
| Year Protection Granted | 2009 |
| Licensed | Yes |
| Impact | improved diagnostic & forensic PCR assays, ancient DNA research |
| Title | M4 Emulsions |
| Description | polymerases with increased ability for mismatch extension, enhanced processivity and expanded substrate spectrum |
| IP Reference | AU2010200031 |
| Protection | Patent granted |
| Year Protection Granted | 2010 |
| Licensed | Yes |
| Impact | Method for the generation of DNA polymerases which exhibit relaxed substrate specificity |
| Description | BBC Discovery program, World service |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Radio interview NA |
| Year(s) Of Engagement Activity | 2010 |
| Description | BBC4 radio program |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Radio science program NA |
| Year(s) Of Engagement Activity | 2010 |
| Description | Cambridge Science Society talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Gave talk at Cambridge Scientific Society with more than 1000 permanent members (and a much larger email database). The Society is a prestigious platform for the first public exposure of new research and findings. Past speakers include Nobel Laureates James Watson, Sir Tim Hunt and Sir John Walker, eminent scientists Sir Roger Penrose, Sir Richard Friend, Sir John Beddington and Peter Atkins, popular author Matt Ridley, and former Universities and Sciences minister David Willetts among many others. Tlk was well received by ca. 100 attendees and prompted many discussions and online Tweets. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.scisoc.com/talks/ |
| Description | New polymerases for old DNA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | talk on "Second Nature", Nature publishings virtual web conference site in Second Life follow up questions from public by e-mail |
| Year(s) Of Engagement Activity | 2008 |
| Description | Orthosome |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | describe FP6 funded project : orthosome on website feedback on project, attract students |
| Year(s) Of Engagement Activity | 2007 |
| Description | Press article |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | phone interview for Guardian article "Biologists join the race to create synthetic life" article |
| Year(s) Of Engagement Activity | 2008 |
| Description | Public lecture |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | New Scientist Instant Expert: Origins and Evolution of Life event at The Royal College of General Practitioners |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.nature.com/natureevents/science/events/58969-New_Scientist_Instant_Expert_The_Origins_of... |
| Description | RSC Policy seminar |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | seminar to public / policymakers about impact and future of synthetic biology interviews with journalists e.g. Today program, Guardian science podcast etc. |
| Year(s) Of Engagement Activity | 2008 |
| Description | RSC discussion meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | RSC 2 day discussion meeting for ca. 120 leading academics, policymakers and other stakeholders RSC published summary booklet |
| Year(s) Of Engagement Activity | 2008 |
| Description | Radio interview (Deutschlandfunk 2013) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | radio interview |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.dradio.de/dlf/sendungen/forschak/2171572/ |
| Description | Royal Society Summer Science Exhibition |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Members of my lab were involved in presenting a stand at the Royal Society Summer Science Exhibition |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talk , LMB Alumni symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | talk sparked question and discussions afterwards increased interest in my research |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www2.mrc-lmb.cam.ac.uk/alumnisymposium/programme.php |
| Description | Talk at Cambridge Synthetic Biology Society |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | Talk at Cambridge Synthetic Biology Society attended by ca. 50-100 students at Pfizer Lecture Theatre at Cambridge University, which sparked questions and discussion afterwards, and an interest in students wishing to join my lab or learn more about our research. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Talk for non-scientific staff |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | talk sparked questions and discussion afterwards better understanding of my research by support staff |
| Year(s) Of Engagement Activity | 2014 |