Sandpit: The Programmable Rhizosphere

Humans have striven for centuries to control and exploit living organisms for their own purposes. Agricultural practices have been developed to maximise the yield of plants and animals. More recently, microbial systems have been manipulated to increase their utility in the food, biotech and brewing industries. Many of these changes have been achieved through breeding and chance selection for improved agronomic characters. Recent developments in genetic engineering have allowed scientists to apply precise perturbations that lead to beneficial changes in an organism. However, the complexity of biological systems makes it difficult to manually design and implement large changes that predictably produce an intended phenotype using conventional genetic engineering techniques. Our ability to synthesise DNA far outstrips our ability to design new genetic systems. Synthetic Biology holds the promise of rational design and reproducible fabrication of biological circuits that can be used to introduce a desired function in an organism. One of the main premises of this approach is that engineering principles should be applied to the design of modular circuits from well-characterized parts and components, using defined composition rules. A framework that enables this approach to the engineering of biology has, to date, been lacking. In this project, we propose to develop such a framework, and a unique library of new DNA parts. Specifically, we propose to tackle the problem of how cellular circuits in organisms (such as microbes and plants) can be designed in to self-organise and interact with other organisms in a predictable and robust fashion. To this end we will develop novel mathematical and computational approaches that automatically transform a quantitative description of a desired function into a circuit design that implements this function in bacteria. In addition we will generate a collection of DNA parts that will allow the construction of new channels of communication between different cell populations or organisms, and the pathways for symbiotic exchange of nutrients. There are many situations where improvements in the ability to regulate cells, and to form stable new ecologies, would be of benefit to humans. These range from applications in tissue engineering through to bioremediation, biotechnology and bioenergy. In this project we have chosen to focus on the relationship between plants and soil bacteria that normally live alongside the root system. We wish to engineer communication between a model bacterium and model plant, to allow negotiation and establishment of a new symbiotic relationship. The system would have many applications for improvements in sustainable agriculture, bioproduction and food security, such as improvements in soil use, pest resistance, weed suppression and creation of new crop plants capable of nitrogen fixation.

Beneficiaries of the research:This is an ambitious project which, if successful, has the potential to impact on many areas of society, including the larger life science and biotechnology community, government and regulatory agencies, and even the agricultural industry. The larger biotechnology community - tools and methodologies: The ability to engineer cellular function in time and space is a critical underlying capability for many applications in biological engineering. Therefore, the successful execution of this research project will provide the foundations for broader efforts in engineering complex biological systems. The experimental and model-based toolchain will be developed as a technology platform, making it universally applicable in bio-based technologies at large, including synthetic biology, systems biology and metabolic engineering. Government / regulatory agencies: All investigators on this project have actively engaged with government and regulatory bodies in the past, including describing the potential impact their research can have towards the economic development of the nation, serving as reviewers on other projects, and as sources of information on issues related to synthetic biology. The results that arise from this project will be an important consideration in the formulation of policies related to synthetic biology applied to agricultural research. Society - awareness, engagement through extension services, and ethical considerations: Over the term of this project, we will direct effort to communicating and sharing our research efforts, goals, and implications to the agricultural stakeholder community, through presentations, informational literature and relevant newsletter articles in conjunction with outreach, education and public engagement exercises. In addition, we are promoting the development and adoption of standards within the biology community. This includes the generation of standardised educational materials for Synthetic Biology and promoting the distribution of strains and protocols for practical teaching. This research will connect to the Edinburgh-Stanford research project on Synthetic Aesthetics, which aims to integrate aesthetic concerns into synthetic biology projects and products, enabling inclusive and responsive technology development. Impact on teaching in the classroom: All investigators teach graduate and undergraduate courses which incorporate elements relevant to their respective research contributions in this project. Outcomes of this research, including tutorials on mathematical modeling of biological systems and design criteria for regulatory systems and communication modules will be incorporated into the courses currently taught by the investigators. Mentoring undergraduates for iGEM: Each investigator actively participates as an adviser in the annual iGEM contest. The project will contribute to the promotion of interdisciplinary educational challenges in Synthetic Biology. Dissemination and exploitation of research results: The following routes will be utilized for the broadest possible dissemination of research results: 1) Publication through scientific journals of the highest quality. 2) Publication through posters, presentations and papers at technical conferences and annual meetings of professional societies such as American Chemical Society and Institute of Biological Engineering. 3) web-based distribution of software and data, 4) Publication of research protocols via OpenWetWare, a Wiki-based system for the sharing of information related to synthetic biology. 5) Servicing requests for genetic materials as per institutional guidelines.