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Synthetic biology sandpit: collaboration between EPSRC and US NSF

Background

Following a successful IDEAS Factory Sandpit earlier this year, the Engineering and Physical Sciences Research Council (EPSRC) in partnership with United States National Science Foundation (NSF) have awarded £6 million to five new research projects in the area of synthetic biology.

This sandpit enabled some of the best researchers from the UK to conceive truly transformative projects with their counterparts in the US. EPSRC first introduced IDEAS Factory Sandpits in 2004 and set out to encourage a generation of transformative research within the UK.

EPSRC and the NSF now have the opportunity to support this research on an international scale and the sandpit mechanism is proving to be successful five years on as highlighted by some of the participant’s comments below:

Jay Keasling, University of California, Berkley: "It was a completely new experience getting instant feedback on proposed work. Not only was the process quick and relatively painless, it was fun. I think that the NSF should use the sandpit process for other areas."

Declan Bates, University of Leicester: “I think the sandpit helped to significantly enlarge and strengthen the synthetic biology community in the UK, both by introducing new members from other disciplines and by initiating new collaborations at national and international level.“

Michael Jewett, Northwestern University: “One of the most intense, creative, and rewarding experiences of my professional career. Never before have I had the opportunity to spend five days of protected time to brainstorm and develop envelope-pushing ideas with amazing scientists from such a diverse cross-section of disciplines. This was such a luxury.”

Paul Freemont, Imperial College London: “I believe that the sandpit has brought together a group of outstanding researchers and allowed them to develop innovative projects which I am certain (some of which) will have a major impact on synthetic biology research. I came away with very positive feelings that have reaffirmed why I chose a research career.”

Public dialogue

EPSRC and BBSRC, with funding from Sciencewise Expert Resource Centre, have commissioned the British Market Research Bureau (BMRB) to conduct a public dialogue on synthetic biology. This dialogue will help frame the issues and promote discussion of those raised by synthetic biology research. This will help the Research Councils and others to ensure that future policies better reflect the views, concerns and aspirations of the public. The Public dialogue aims to allow the diverse perspectives of a range of UK residents to be articulated clearly and in public in order that future policies can better reflect these views, concerns and aspirations.

Summary of research projects

Synthetic integrons for continuous directed evolution of complex genetic ensembles
UK partners: University of Glasgow, John Innes Centre, Imperial College London, University of Leicester
US partners: Northwestern University, University of California, Berkeley

A grand challenge in the field of synthetic biology is the need for technologies that enable the construction of novel and complex functions in biological systems. When these functions involve the expression and coordination of multiple genes, building them becomes increasingly difficult. Nature has however evolved mechanisms to deal with such complexity.

This research project will develop a synthetic system that harnesses the power of these natural mechanisms to enable synthetic biologists to generate, diversify, and refine complex multigenic functions. The core of this technology will be based on a bacterial innovation called integrons, which are natural cloning and expression systems that assemble multiple open reading frames, in the form of gene cassettes, by using site-specific recombination and conversion to functional genes by expression from an internal promoter.

This project will generate a robust technology enabling the engineering of biological systems, including both microbes and plants, for myriad useful purposes. Notable examples include the production of renewable bio-fuels and biomaterials, the synthesis of small biomolecules for applications in specialty chemicals, bioremediation, and improvement of crops for agriculture. This project will also provide a scientific tool for probing genome organization and dynamics in processes such as the emergence of microbial resistance to small-molecules and metabolic pathway evolution.

Synthetics aesthetics: connecting synthetic biology and creative design
UK: University of Edinburgh
US: Stanford University

The Synthetic Aesthetics project will bring together scientists and engineers who are developing and applying powerful new tools for engineering biology with artists and design professionals who are expert at creating beautiful objects. The project will explore how the tools of genetic engineering and biotechnology can be adapted and extended in service of creative design processes, broadly defined.

In the first stage we will develop case studies summarising work in synthetic biology to distribute to the creative professionals. We will also identify groups and individuals who would benefit from being part of the project. We will bring in a consultant at this stage to help us form links with the creative and design communities. In stage two, we will arrange twelve two-week long exchanges where members of both communities spend time in each others' institutions. The post-doctoral fellow will facilitate and analyse these exchanges. In the third stage, we will organise two launch workshops: one at a synthetic biology conference and one at a design conference. We will also develop web resources and other dissemination mechanisms, to ensure that the results of the research reach a broad audience.

We hope to see a surge of growth and interest in the aesthetics of synthetic biology in the final phase, which will influence teaching, research and product development. This could lead to new forms of engineering and new schools of art, as well as new ways for the public to engage with synthetic biology.

Engineering genetically augmented polymers (GAPS)
UK: University of Bristol, University of Warwick
US: University of Texas at Austin, Northwestern University

Nature constructs beautiful and complex living entities using a surprisingly small array of different building blocks. Whilst we know what the essential building blocks are, we have yet to understand the intricacy of how they are brought together and assembled in Nature. There is tremendous potential to tap into this knowledge.

We propose to tap into Nature's coding information; the genetic information stored in an organism's DNA. The information is stored very precisely in DNA and is transferred and used very efficiently during growth and development to give healthy organisms with certain characteristics and abilities. We want to use this genetic information to programme the interaction of natural and chemical systems. This will give a great deal of control during the engineering of new materials and devices, as we can precisely combine the components. This type of precision and programming has been lacking from such endeavours thus far.

This work will give us an entirely new way to design and build materials. We will be able to instruct specific biological modules to interact and cooperate in precise ways with materials like plastics. This will be very different from how our everyday technologies are currently built as we lack this programming ability. It will provide components and construction methods for the engineering and manufacture of drugs, materials and devices.

In addition to creating a wholly new ur-cell platform for synthetic biology applications, the formation of a strong a UK-US team will have a considerable impact on the global leadership by these two countries in synthetic biology. The readily grasped goals of this project (programmable cells, replicating plastic) will provide opportunities for showing the public that synthetic biology is a field that yields translational technologies that can impact their own lives. Following up on the goals of the Sandpit, the international research team will establish and maintain a valuable network that provides for competitive, interdisciplinary, and globally-engaged research.

Cyberplasm: An autonomous micro-robot constructed using synthetic biology
UK: Newcastle University
US: Northeastern University

The aim of this proposal is to construct Cyberplasm, a micro-scale robot using principles of synthetic biology. This will be accomplished using a combination of advanced microelectronics and biomimicry; an approach that mimics animal models; in the latter we will imitate some of the behaviour of the marine animal the sea lamprey. Synthetic muscle will propel the robot through liquid. Synthetic sensors derived from yeast cells will be reporting signals from the immediate environment. These signals will be processed by an electronic nervous system. The electronic brain will, in turn, generate signals to drive the muscle cells that will use glucose for energy. All electronic components will be powered by a microbial fuel cell integrated into the robot body.

The development of Cyberplasm will impact the imagination of the general public, the private sector, and education in general. The robotics industry (in terms of biotech, healthcare, agriculture and healthcare) is worth billions of dollars annually. A hybrid bio/synthetic robot would completely revolutionize aspects of this industry allowing robots to operate with a whole new level of control and functionality. Amongst the fundamental issues that this research addresses is the integration of bacteria into fuel cells, as well as yeast and mammalian cells into engineered devices such as sensors and actuators, respectively. Moreover, we will address the I/O problem by developing mechanisms for these engineered cells to communicate with electronics.

Programming the rhizosphere through highly integrated genetic, spatiotemporal control systems
UK: University of Cambridge, Newcastle University
US: University of Illinios at Urbana-Champaign, University of California, San Francisco, Stanford

Humans have striven for centuries to control and exploit living organisms for their own purposes. 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.

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. 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.