HNAEPISOME
Directed evolution of a synthetic episome based on hexitol nucleic acids (HNA)
| Coordinatore | UNIVERSITY COLLEGE LONDON
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 1˙188˙594 € |
| EC contributo | 1˙188˙594 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2013-StG |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-02-01 - 2018-01-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
UNIVERSITY COLLEGE LONDON
Organization address
address: GOWER STREET contact info |
UK (LONDON) | hostInstitution | 1˙188˙594.00 |
| 2 |
UNIVERSITY COLLEGE LONDON
Organization address
address: GOWER STREET contact info |
UK (LONDON) | hostInstitution | 1˙188˙594.00 |
Mappa
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Obiettivo del progetto (Objective)
'A long term goal of synthetic biology is the assembly of a cell from its individual components. A genetic element based on synthetic nucleic acids capable of stable propagation, a synthetic episome, is the minimal genetic element required for the systematic development of all cellular components of a synthetic organism based on artificial nucleic acids. Recent progress in DNA polymerase engineering has successfully isolated variants with expanded substrate spectra capable of efficiently synthesising hexitol nucleic acids (HNA) from DNA templates, and capable of synthesising DNA from HNA templates. Together, they demonstrate that HNA can serve as a genetic material. However, the unavoidable DNA intermediate in HNA replication and their limited processivity greatly limit the potential of these polymerases for the development of an HNA episome.
To establish an HNA episome, processive HNA-directed HNA polymerases as well as accessory proteins to support episome maintenance and replication are required. The bacteriophage phi29 requires only four proteins (including polymerase, terminal protein, single-stranded and double-stranded DNA binding proteins) and two DNA elements (origin of replication and high affinity sites for its double-stranded DNA binding protein) to replicate and maintain its linear genome, making it a suitable starting point for the development of an HNA episome.
We propose to develop novel in vitro selection methodologies that will allow the directed evolution of a minimal HNA episome based on the phi29 system – including the isolation of an HNA-dependent HNA polymerase, a modified terminal protein and single-stranded as well as double-stranded HNA binding proteins. In addition to being a landmark result in synthetic biology, such HNA episome can form the basis of safer genetically modified organisms, in which the traits are encoded outside biology in an HNA episome dependent on the continued supply of artificial substrates for its maintenance.'