Self-disclosing protective materials using synthetic gene networks

Materials that have the ability to accurately report their current condition or their historical exposure to chemical, biological or other events, offer immense value in enhancing the decision making capabilities of the user. This may be, for example, a fabric that changes colour in the presence of a particular chemical, a gel that alters its viscosity to indicate the early onset of metal corrosion, or a strip of paper that self-destructs in the presence of a biological cue. This ability is even more valuable if it augments current infrastructure without requiring re-modelling of equipment and working practises. In an ideal world such devices are passive - not necessitating any input from the user until, or unless, they are required to 'self-disclose'. Finally, given that transportation costs are a major expense in any field deployment, it is crucial that the ability to functionalise materials does not incur any additional weight penalty.

In this project we are seeking to exploit the increasing ability of bioengineers to develop novel stimuli-responsive gene networks - inspired by the genetic diversity of biological species - and embed these systems in functional materials. Genetic circuits afford key benefits for this application: they are lightweight, they can be encoded to react to a range of provocations, and they can output colour changes or other easily perceived properties to signal that insult has occurred. Moreover, gene circuitry is encoded in DNA. Advances over the last decade have obviated the need for traditional gene cloning, meaning that almost any DNA sequence, natural or synthetic, can be chemically synthesised and assembled quickly. In conjunction with our experience of cell-free gene expression, this offers an unparalleled opportunity to explore the relationship between DNA sequence and function. This technological platform could therefore be used to develop any number of devices with the capability to respond to a wide range of stimuli, with applications in the defence of both military and civilian populations.

Our aim is to use these technologies to build and optimise several proof of concept (PoC) synthetic gene networks in materials such as paper and hydrogels, with the longer term aim of being able to functionalise protective materials such as cardboard (for use in pop-up shelters, for example) and hydrogels (to allow the smart finishing of textiles and adhesives, for example). Of particular interest is the potential for combining two highly sensitive and tunable technologies: synthetic gene networks (SGNs) with stimuli responsive hydrogels. This is because, whilst stimuli responsive hydrogels offer great potential on their own, the range of stimuli to which they respond does not offer the variety and subtlety that biological systems possess. Building composite SGN/hydrogel devices, where information flows from SGN to hydrogel and back, provides an exciting opportunity for synergy between the two technologies.

However, whilst these technologies will be developed within controlled laboratory conditions, the eventual aim is for their deployment in the wider world. This raises two issues: the first is practical - how will these devices operate in variable conditions, away from the protection of the experimental scientist; and second - what is our response to the use of synthetic gene networks outside of an experimental situation? Can we ensure that safety of these devices is central to their design from the point of project initiation? This project will address these two issues. We will set safety standards for novel gene that can be used in this project and in the wider synthetic biology community; and we will continue to engage with relevant stakeholders (e.g.Dstl, Synthace and appropriate commercial partners) to better understand the roadblocks to translation.

Scientific advances:
Firstly, the scientific community, in particular synthetic biologists, polymer scientists and statisticians will benefit. This project will combine synthetic biology and polymer sciences in an experimental framework that will enable statistical exploration and exploitation of the design space. The synthetic biology community will benefit from novel approaches to gene construct design and optimisation that we believe will stimulate efforts to design genetic devices beyond the dominant cut-and-paste concept. The impacts will also flow in the opposite direction. By enabling functional gene networks to be embedded in, and interact with, polymers, we will increase the diversity and functionality of polymer chemistry. By implementing a predictive statistical modelling approach we will inform the statistical and machine learning communities of the opportunities and challenges involved in engineering complex, highly interacting systems. Finally, by providing an iterative wet-laboratory platform to support this endeavour, we provide the experimental tools to test and validate their approaches.

Industrial Research and Development, and Commercial Products:
Secondly, we believe that there is a potential for impact in commercial manufacturing sectors, and that this can lead to significant inward investment for the UK. This project seeks to embed synthetic gene networks (SGNs), safely and robustly, into functional materials. One of our target materials are the hydrogels. Hydrogels are commercially manufactured and utilised in a wide-range of applications, from adhesives, medical devices, protective clothing, detergent products, composts, and nappies and they are being developed for use in smart windows and tough fabrics. By developing a design platform and proof-of-concept for SGN-enabled hydrogels this project can inspire new commercial opportunities in this area.

Societal:
Thirdly, there is considerable scope for public and commercial engagement around issues of safety and responsible innovation in the design of biological, or biologically-derived, devices. We believe that this project can deliver tangible results demonstrating how safety can be incorporated at the start of the design process. As a result data generated in this project can provide a focus for discussions that move beyond this project, such as: how do we, as scientists or the myriad publics, respond to the use of synthetic gene networks in inert objects? How do we build safety or acceptance concerns into the design of biological devices, including genetically modified organisms (GMOs)?

Skills and capabilities:
Finally, there is considerable scope for professional development and capacity building in the UK science base. This project is at heart an interdisciplinary venture. Moreover, the PI and CoIs have a track record of successful industry engagement. This contributes to the foundational science and engineering capabilities that were identified in the 2012 'Synthetic biology roadmap for the UK' and provides a skilled and energised workforce.