Aims of the Biomaker initiative
The field of Synthetic Biology is introducing low-cost, breakthrough technologies for a wide range of practical challenges including diagnostics, environmental conservation, microbial bioproduction, crop improvement and human health. These are of critical importance to the future well-being and economic development of sustainable societies across the planet.
Synthetic Biology is adopting technical engineering approaches for the reprogramming of biological systems, including: (i) the introduction of standardised, modular DNA parts and new methods for rapid assembly of synthetic genetic circuits, (ii) new legal frameworks, repositories and open source technologies for the free exchange of genetic components, (iii) Production of simple, DNA-programmable cell free expression systems that can be freeze-dried, shipped and stored without refrigeration. These are GMO-free and can be used in the field or classroom without expensive facilities or elaborate containment, and (iv) systems for transient gene expression in contained hosts, and transgene-free genome editing to reduce the costs, resources and regulatory hurdles associated with the deployment of genetically modified organisms.
The Biomaker programme provides funding for project-based learning at the intersection of electronics, 3D printing, sensor technology, low cost DIY instrumentation and biology. Biomaker aims to build open tools and promote development of research skills and interdisciplinary collaborations. The programme is being built in three stages. First, we are exploiting existing open standards and a rich ecosystem of resources for microcontrollers, first established to simplify programming and physical computing for designers, artists and scientists. These resources provide a simple environment for biologists to learn programming and hardware skills, and develop real-world laboratory tools. Further, the Biomaker projects provide a direct route for physical scientists and engineers to get hands-on experience with biological systems. Second, we will introduce cell-free systems to implement DNA programming in a way that is low-cost and easy to implement. Third, we will develop appliances and open curricula for worldwide use.
Synthetic Biology technologies are relatively low-cost, but their adoption is often limited by deficits in technical training, poor access to new research materials, inadequate laboratory facilities, and lack of strategic partnerships with leading research institutions. We aim to develop tools for improved synthetic biology training in schools, universities, community labs and industry. We believe that efforts to develop open standards and protocols for DNA parts and low-cost DIY tools will provide a major impetus for democratisation of this new technology, and facile transfer from richer to poorer countries.
The Biomaker initiative funds small-scale projects at the intersection of the new biology and other sciences, in order to engineer low-cost tools, real-world applications and explore policy development.
Biotechnology is fertile ground for international exchange, and capacity-building based on open technologies and exchange should be a major component of any funding initiative. Synthetic biology can provide better solutions for: (i) rapid-response production of vaccines and biologics, (ii) point-of-use diagnostics and field biosensors, (iii) agricultural crop improvement using non-transgenic (genome editing) tools, and (iv) harnessing local biodiversity to build a sustainable bioeconomy.
In each of these applications, the development of practical solutions and social impact requires: Shared curricula for training and biotechnology education in resource-poor communities and institutes; Building local expertise through exchange and shared knowledge; and Establishing in-country facilities for generation and exchange of open-source tools and materials.
For a number of years, we have run teams for interdisciplinary project-based learning in Cambridge. Despite best of intentions, interdisciplinary teams will fractionate into “dry” and" “wet” parts of a shared engineering project, with a split between biologists and engineers/physical scientists. Biomaker is based on the conviction that there are ways of breaking down barriers between scientific and engineering disciplines, and barriers between institutes and countries - and we have incorporated these new approaches:
Simple unified hardware platform
We have developed a cost-effective Biomaker hardware platform that can be given as a starter kit for teams and individuals. This provides a common starting platform for projects, and facilitates sharing of resources. We chose an Arduino-compatible microcontroller platform for access the widest range of open source hardware and software resources. In addition, microcontrollers are easier to program and use, without the complications of operating systems and with non-volatile memory allowing their use as “plug-and-go”, instantly accessible devices.
Graphical dataflow programming
We have established workflows and new resources for device programming using XOD, a new open source environment for graphical programming of Arduino platforms. XOD employs a dataflow model where program elements are available as nodes. This is different from most Arduino-compatible graphical programming environments, which are based on MIT Scratch and use pictorial blocks to create conventional program loops. XOD nodes are laid out onscreen and the flow of information through the logic circuit is “wired”. Low level nodes or external code can be easily encapsulated into single nodes, so complex logic or interfaces can be encapsulated and unecessary detail can be hidden from the user. Completed programs (termed patches) can be downloaded to a connected microcontroller board, tested and debugged interactively. This way of working is familiar to the molecular biologist, who will lay out a genetic circuit, map out molecular interactions between the components, build the DNA circuit, implement it in a transformed cell, and measure the performance of the circuit using genetic markers (flags) and analytical techniques, perhaps with several repeated cycles of debugging.
Sophisticated user interfaces
We utility of the microcontroller platform is vastly expanded by the use of accessible displays and devices for interaction. The Biomaker Starter Kit provides wide range of display and switch components. A highlight is the provision of a 4D Systems programmable touchscreen display that can be used to build sophisticated user interfaces. The manufacturer provides free software for “drag-and-drop” assembly of custom user interfaces, from a given library of user interface elements. The custom interface can be loaded into the touchscreen, and we have supported the production of XOD code that allows non-programmers to build bespoke high-level user interfaces.
We continue to provide resources for flexible assembly of custom chassis and housings for new instruments. These include files for 3D printed components, including lens, camera and fibre optic carriers for optictical instruments, and beam systems like Totemmaker for flexible construction of chassis.
Free web-based platform for documentation and project portfolios
We have established a web-based platform for project documentation (https://www.hackster.io/biomaker) which allows us to promote international sharing and project collaboration.
We have short term pump-priming funding to run Biomaker in Cambridge-Norwich this year - with a number of international partners (Kumasi, Ghana; Pretoria, South Africa; Mansour, Egypt; Bahir Dar, Ethiopia; Adelaide, Australia and beyond)
Need for capacity building
Synthetic biology and open-source applied biology tools that are pragmatic, safe and cost-effective have the potential to stimulate bioeconomic growth and address African challenges in healthcare, agriculture, education and the environment. OpenPlant and Biomaker principals helped to organise a symposium and workshop in Pretoria and Bakubung, South Africa in 2017, supported by the UK Global Challenges Research Fund (GCRF). This resulted in the Bakubung report on “Capacity building for the bioeconomy in Africa”, that describes the latest developments in synthetic biology, bioengineering and DIY biology, their potential as training tools for students and future innovators, and practical opportunities for deployment in Africa. The study concluded that:
Synthetic biology offers new tools and approaches:
Standardised, modular DNA parts and rapid assembly of genetic circuits for reprogramming biological systems.
Cell free expression systems that do not require containment, and can be freeze-dried and stored at ambient temperatures to eliminate the need for refrigeration.
Transient gene expression in contained hosts, and transgene-free genome editing to avoid the costs, resources and regulatory hurdles associated with the deployment of genetically modified organisms.
Legal frameworks, repositories and open technologies for the open exchange of genetic materials.
These new technologies are relatively low-cost and provide major opportunities for innovation and benefit, but their adoption is often limited by deficits in technical training, poor access to new research materials, inadequate laboratory facilities, and lack of strategic partnerships. This is a global prospect , not limited to African countries.
We all share a common goal with the need to develop improved synthetic biology training in schools, universities, community labs and industry, and international efforts to develop open standards and protocols for DNA parts and tools will provide a major impetus for technology transfer. We think that (i) biotechnology is fertile area for international exchange, and that (ii) capacity-building based on open technologies and exchange will be a major factor in promoting innovation.
Synthetic biology can provide better solutions for: (i) rapid-response production of vaccines and biologics, (ii) point-of-use diagnostics and field biosensors, (iii) agricultural crop improvement using non-transgenic (genome editing) tools, and (iv) harnessing local biodiversity to build a sustainable bioeconomy. The development of practical solutions and social impact in these areas requires:
Building local interdisciplinary expertise through exchange and shared knowledge.
Establishing mechanisms for generation and exchange of open-source tools and materials.
Standardised curricula for training and biotechnology education, especially in resource-poor communities and institutes.
Biomaker takes off
The Biomaker programme has been funded from a variety of sources, starting with £90K support for mini-projects by a Strategic Research Initiative for Synthetic Biology at the University of Cambridge (http://www.synbio.cam.ac.uk) in 2014-2015. This was followed by £500K support from the BBSRC/EPSRC OpenPlant Synthetic Biology Research Centre (https://www.openplant.org) for OpenPlant and Biomaker projects in 2014-2019. These allowed the creation of new interdisciplinary team projects across Cambridge and Norwich with seed funding for each team. Every six months, a call is launched for innovative projects that will bring new people and ideas together. Teams are required to make a short application for funding, for a project that must lead to tangible, publicly documented and open outcomes, which could include (but are not limited to): design files and prototype for a hardware project, software development and documentation, a white paper arising from a workshop, (iv) educational resource or synthesis and sharing of useful DNA parts or vectors. We look for short-term projects that might be completed in a roughly six-month period.
The teams are usually made up of graduate students or postdoctoral workers, but have included undergraduate teams and faculty. They must have agreement from their supervisor and institutional cost-code holder that the proposed project and management of the allocated funding will fit with their existing work. The teams must pitch their idea to their peers and a team of judges. The projects are ranked, evaluated for the prospect of tangible outcomes that can be readily shared, promotion of interdisciplinary working and exchange, relevance to synthetic biology, open technologies and responsible innovation, realistic scope for timing, costing and the proposed team, and evidence for any external collaborations and matching support.
To date, we have funded around 140 mini-projects, with overwhelmingly positive outcomes for interdisciplinary collaboration, sharing and propagation of research tools and training, and production of open tools for innovation. We have found that the development of bioinstrumentation is an efficient way of promoting cross-over between biology and the physical sciences, computing and engineering. In 2017 we developed a new model, the Biomaker Challenge, to provide a lower cost and more portable way of expanding this programme.
The Biomaker Challenge is based on a £100 Starter Kit for bioinstrumentation, which is designed to allow biologists, who might be unfamiliar with electronics and programming, to collaborate share trading with scientists and engineers, who have little experience with biological systems. The Starter Kit is based on simple, open Arduino technology and resources (http://www.arduino.cc), and includes training resources that require no prior knowledge of the system. It includes a comprehensive prototyping environment and a 4D Systems programmable touchscreen for the creation of sophisticated portable user interfaces and displays. The teams have time to develop their devices, document these on Github and Hackster, and come together as part of a public exhibition of open technology, the Biomaker Fayre in Cambridge. We hope that this streamlined model for developing interdisciplinary exchange will be of wider interest, and we looking for ways to develop international collaborations. We believe that this model provides new opportunities to develop and share low-cost tools for biological research and teaching.
Scope for biology
Recent technical advances in the preparation of microbial cell-free extracts have given rise to a new class of highly efficient systems for gene expression that are cheap to deploy and have huge potential benefit for the provision of a wide variety of diagnostics, sensors, vaccines and research materials. Further, the extracts can be stored desiccated, stable for over a year, and reactivated at the point of use by hydration. The cell free extracts can be programmed by the addition of DNA to allow rapid and simple prototyping of gene circuits for diagnostics or bioproduction.
In vitro biology provides a number of key advantages for the design, assembly and testing of DNA encoded circuits for diagnostics and environmental sensing. Cell-free extracts avoid the complications, delays and regulatory uncertainty associated with uncontained of GMOs, while providing opportunities for high level, low cost training and capacity building. The emerging technology enables engineering of DNA circuits without the need for genetic modification and in a low cost manner that makes it accessible for researchers in low resource settings.
Biomaker is sponsoring efforts to integrate cell-free biology materials into future Starter Kits, and to promote programmatic approaches to biology for practical application and training. We are assembling two expansion kits for (i) lab-based bio-measurements, involving tube and paper-based reactions with optical outputs with a kits of sensors, holders, plastic fibre optics, temperature control, etc., and (ii) environmental measurements with sensors, transmitters, loggers, motors and pumps for actuation, etc. Longer term plans for 2020-21 include a plan for an expansion kit for low-cost macroscopy/microscopy with opportunities for machine learning, and new customised hardware with integrated touchscreen and new sensors.
Open curriculum development
The field of Synthetic Biology has pioneered the adoption of standardised and modular approaches to reprogramming biological systems. We believe that the combination of commodity electronics and optics with cell-free biological systems will enable radically different approaches to the teaching of this "new biology", and will allow the development of a new generation of curriculum materials for project-based learning, that are both cheap and highly accessible for students who might otherwise be excluded from engaging with this topic. We believe that efforts like the Biomaker Challenge are needed to underpin interdisciplinary innovation that will be at the heart of the biology-based sustainable technologies of the coming century - and to facilitate and democratise global access to innovation in the bioeconomy.
Prof Jim Haseloff, University of Cambridge