One of the aims of Synthetic Biology is to build complex bio-machines using the simple building blocks of life. This includes developing complex genetic circuits from much simpler promoters and regulators, complex biosynthetic pathways from collections of enzymes and novel nanoparticles from assemblies of DNA or proteins. In this project we aim to explore how viruses can be used as components in bionanoassembly.
As part of a collaboration between the University of Birmingham (Professor T. Dafforn) and UCL (Professor J. Ward) we have now begun to use bacteriophage M13 as a synthetic biology chassis to address a number of other applications. These have included exploring whether M13 can be assembled to form new materials and structures that can be applied to applications from bioelectronics and photonics to liquid crystals. One startling success from this work has been the generation of intellectual property based on the use of dye-linked M13 particles in a novel laser system.
Elsewhere in the world M13 is now being used as a particle of choice in a number of systems. For example work by Belcher and colleagues at MIT have shown that M13 can be used to in photovoltaic devices and as nanowires, while Cha and colleagues at U. Colorado have shown that DNA can be attached to the M13 case and used as a novel DNA detection system.
The burgeoning growth in the use of M13 as a chemically flexible bionanoscaffold is inevitably leading to an increase in requirement for the material itself. In this project we aim to begin to address the problem of industrialising the production of M13.
Currently M13 is made as a product of E. coli culture (E. coli is the host for M13) with the virus being purified by precipitation and centrifugation protocols that are decades old and suitable only for milligramme scale production. UCL have led the way in recent years in the development of new methods for producing M13 which have shown that there is significant room to improve the process. However the process still lacks scaleability.
In this project we will develop protocols that allow the scale up of M13 production. This will include:
1) Development of “safe” M13 phages that can only replicate in the presence of a specific E. coli strain. This allows M13 production to be carried out in commercial fementors without the risk of cross-contamination with future fermentations.
2) Development of downstream methods that can be used to produce M13 at gram scale
3) Assessment of other filamentous bacteriophages in terms of yield, stability and functionality to widen the number of materials available to users.
This project is funded by the Midlands Integrative Biosciences Training Partnership (MIBTP), a BBSRC-funded doctoral training partnership between the universities of Warwick, Birmingham and Leicester.
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Chen PY, Hyder MN, Mackanic D, Courchesne NM, Qi J, Klug MT, Belcher AM, Hammond PT. Assembly of viral hydrogels for three-dimensional conducting nanocomposites. Adv Mater. 2014 Aug 13;26(30):5101-7.
Courchesne NM, Klug MT, Chen PY, Kooi SE, Yun DS, Hong N, Fang NX, Belcher AM, Hammond PT. Assembly of a bacteriophage-based template for the organization of materials into nanoporous networks. Adv Mater. 2014 Jun 4;26(21):3398-404