Synthetic Portabolomics: Leading the way at the crossroads of the Digital and the Bio Economies

Lead Research Organisation: Newcastle University
Department Name: Sch of Computing

Abstract

Synthetic biology involves the design and development of novel, useful biological systems, or the redesign of those systems that exist already. This approach promises to be of major value to society. Potential applications include the production of high-value materials, such as fine chemicals and pharmaceuticals, bio-remediation, sustainable energy, medical diagnostics, and agriculture.

In Synthetic Biology novel biological genetic circuits are developed using engineering principles in order to add the new properties to a given organism - called a host or chassis. The type of chassis used will vary according to the application and the circuit. For example, for food and agriculture it is highly desirable to use organisms that have been shown to be safe for human consumption. However, currently, most circuits are designed for, and tested in, a single organism such as the commonly used bacterium Escherichia coli. Moving these circuits to another organism requires the circuit to be re-engineered and retested in the new organism, a process which is very time consuming and costly. This process of 'refactoring' slows down research and costs industry a huge amount of time, effort and money.

A major problem is that the connections between the designed genetic circuit and the chassis organism are specific to a given species of chassis. So the genetic circuit ends up being redesigned to meet the new connections required for a different species. In our project we will standardise the connection between a given genetic circuit and the chassis organism. We will develop a set of academically and industrially useful organisms where the plug-in points for the genetic circuit will be the same for each of our organisms, allowing the genetic circuit to be moved from one organism to another with changes. We refer to this standardised plug-in system as a 'bio-adaptor'.

This programme grant will initiate a new field in Synthetic Biology, called 'Portabolomics'. This is a highly novel approach that has not been achieved by any other groups to-date. The key to the success of the project is to understand the networks of molecular processes that occur in a cell, since it is these networks that will need to be modified to make the bio-adaptor. We will apply a range of the state-of-the-art computing approaches to this task including many techniques from Computing Science, including network analysis, formal methods and data mining, for which our group has a wide range of world-leading expertise.

The results of the Portabolomics project will not only be a new system of major value to UK synthetic biology research and industry, but will enhance the field of computing science as new computational techniques will need to be developed to achieve our goals.

Planned Impact

Synthetic Biology promises to substantially contribute to the UK economy and society. The Chancellor of the Exchequer G. Osborne estimated that the "global synthetic biology market is predicted to grow to £11 billion by 2016". The potential benefits of this rapidly growing field are detailed in a number of key documents including the UK Synthetic Biology Roadmap and the Royal Society Engineering report.

The Portabolomics project, once in place, will try to ensure the widest possible economic and societal impact from the research and resources it will generate. Since we are generating a new field for the synthetic biology community, a large amount of impact will fall into the domain of academic beneficiaries and is discussed above.

However, the key outputs emerging from the project will impact on industry directly. The new Portabolomics enabled chassis, our Portabolomics design specifications and standards, and our software systems will have the most immediate impact on industry. The translation of these outputs will be carried out initially with our industrial partners but will be widened through interactions with other organisations such as SynCiTE and CPI (see pathways to impact section). The biological outputs of the project will be of direct value to these partners as described in the main document (see Strand 2 of Pathways to Impact).

The novel computational approaches to the analysis of complex systems we develop will result in novel approaches for the computational design of synthetic biological systems that will be of clear commercial value in related fields such as neuroscience. Furthermore, this project will develop a wide range of novel research outputs in the fields of computing science. These outputs will be generically applicable, not only in the computing industry but in any other fields requiring advanced data mining strategies for Big Data and network approaches, such as distributed computing and network technology.

More widely, the work of his project in closing key gaps in our knowledge of bacterial processes at the molecular level will impact directly on the process of Synthetic Biology. In turn, this impact on how Synthetic Biology is done will open up new avenues for product development and the application of Synthetic Biology in a wide range of industrial domains. Moreover, the outputs of the project will enhance the capacity of Synthetic Biology to meet the next generation of challenges in a much wider range of fields such as those outlined in the UK Synthetic Biology roadmap.

The project will also have a strong impact on the general public. Our proposed SynBioSmith Sandbox (see Pathways to Impact, strand 5) will allow the general public to carry out synthetic biology experiments without needing to be present in a laboratory. This system will provide enthusiasts such as the DIY Bio movement with an enhanced understanding of the methodology behind synthetic biology and provide access to equipment in a safe and controlled environment. Our vision is to allow the general public to carry out Synthetic Biology over the Internet in a controlled and well-regulated manner making simple Synthetic Biology accessible to everyone. Further impact on the general public will be mediated by the Responsible Innovation section of our project (see strand 1 of the Pathways to Impact), and will allow social scientists will be able to reach out to a broad range of stake holders (scientists, industrialist, NGO, Government and the public).

Publications

10 25 50
 
Description In Synthetic Biology novel biological functionality is developed using sound computational and engineering principles in order to add new properties to a given organism - called a host or chassis. The type of chassis used will vary according to the application and the circuit.

However, currently, most research innovations are designed for, and tested in, model organisms such as the commonly used bacteria Escherichia coli or Bacillus Subtilis.

Moving these circuits to another organism requires the circuit to be re-engineered and re-tested, a process which is very time consuming and costly. This process of 're-coding' slows down research and costs industry a huge amount of time, effort and money. Our international team of world leading researchers are developing a new field in Synthetic Biology, termed 'Portabolomics'. We are taking a novel approach to standardise the connection between a given genetic circuit and the chassis organism by the development of a 'bio-adapter'. This will negate the need to re-engineer and re-test the circuit when moving it to another organism (or chassis).

Portabolomics is at the crossroads of the digital and bio economies and a true breakthrough in the portability of living systems - we want synthetic biologists to be able to engineer new microbial systems in the lab and then port these directly into another species on a large scale without the risk of any unpredictable outcomes.

A range of state-of-the-art computing approaches will be applied to understand the networks of molecular processes that occur in a bacterial cell. Together with our wet lab expertise in bacterial replication, transcription and translation we hope to develop a new system of major value to synthetic biology research and industry.

In parallel researchers in our team will explore the ethical, legal and social issues to inform a responsible design process for current and future work.

Jointly funded by the Engineering and Physical Sciences Research Council (EPSRC), Newcastle University and industry, the £7.5million project will investigate how advances in the Digital Economy and Synthetic Biology could be synergised to engineer new living systems that behave in a predictable way in order to make industrial uptake easier.
Exploitation Route Too early to say (only 1st year of operation out of 5)
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://portabolomics.ico2s.org/
 
Description Capital Award: Quantification for frontier engineering
Amount £100,000 (GBP)
Funding ID EP/S017968/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 03/2020
 
Description Engineering Data Structures Organoids (EnDROIDS)
Amount £2,700,000 (GBP)
Funding ID Chair in Emerging Technologies 
Organisation Royal Academy of Engineering 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2020 
End 02/2030
 
Description Multiscale characterization of complex materials using a combination of atomic force microscopy and optical coherence tomography
Amount £487,050 (GBP)
Funding ID EP/R025606/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 04/2020
 
Description New ways of transcription regulation learned from cyanobacteria
Amount £300,000 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2018 
End 10/2021
 
Description Non-canonical RNA capping in bacteria and human mitochondria
Amount £300,000 (GBP)
Funding ID RPG-2018-437 
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2019 
End 06/2022
 
Title Simbiotics 
Description Simbiotics is a 3D simulation tool offering a range of modelling features to describe bacterial populations. Bacterial cells are represented as discrete geometric entities which may have internal processes and interact with their environment. Modellers may describe specific bacterial behaviour, environmental factors and the spatial arrangement of cellular populations, this is achieved via composing library modules into a model specification. Modules describe specific features to be simulated and are parameterisable, the library is extendable to allow for novel models of relevant processes to be added to the tool. Simulations can be run on mulit-threaded and multi-CPU environments to ensure the platform can represent industrially relevant systems. Simbiotics can be initialised via common standards experimentalists use such as microscopy image data and SBML models, allowing for the rapid development of 3D population models. An optional live 3D rendering and data graphing is available, alternatively exporting data in common formats (CSV and JSON) allow for the integration of Simbiotics into existing tools such as Blender or PovRay. The tool requires minimal programming experience to use. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact N/A 
URL http://ico2s.org/software/simbiotics.html
 
Title Version Control System for Strain Engineering 
Description As DNA sequencing and synthesis become cheaper and more easily accessible, the scale and complexity of biological engineering projects is set to grow. Yet, although there is an accelerating convergence between biotechnology and computing science, a deficit in software and laboratory techniques diminishes the ability to make biotechnology more agile, reproducible and transparent while, at the same time, limiting the security and safety of synthetic biology constructs. To partially address some of these problems, this paper presents an approach for physically linking engineered cells to their digital footprint - we called it digital twinning. This enables the tracking of the entire engineering history of a cell line in a specialised version control system for collaborative strain engineering via simple barcoding protocols. We implemented this as a web application. We used CellRepo to document the key milestones throughout the process of cell engineering, characterisation and barcoding described earlier. 
Type Of Technology Webtool/Application 
Year Produced 2020 
Impact We are exploring routes for commercialisation of an enhanced version of this software 
URL https://cellrepo.ico2s.org/
 
Description Cafe Scientifique (popular science talk to public) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Café Scientifique is a popular science talk format aimed at the general public. It is embedded within the Café Culture series at Newcastle. It provides a show-case for research and an opportunity for the general public to ask questions and debate issues.
Year(s) Of Engagement Activity 2018
 
Description Engagement with night-time visitors to the Great North Museum 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact PEALS researcher, Ken Taylor, and his Portabolomics colleague Dr Emanuela Torelli, took part in the Great North Museum (GNM) European Researcher's Evening on September 27th.

The GNM opened its doors to visitors for an evening event at which University research is presented at stands at different points among the museum collections. There are also short presentations by the researchers.

The event consisted of two short presentations: 1) on DNA and RNA origami research and 2) work on responsible research and innovation. Both talks were well received, and the stand attracted attention from around a quarter of all the visitors.
Year(s) Of Engagement Activity 2019
 
Description Gallery exhibition of artwork linked toresearch project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Hatton Gallery Exhibition: Origins & Endings - this included some original artwork by Marianne Wilde that was inspired by synthetic biology - the opening night was attended by 150 + people and provoked interest and discussion in our research. The exhibition is open until March 2020.
Year(s) Of Engagement Activity 2020
URL https://www.ncl.ac.uk/peals/events/item/hattongalleryexhibition.html
 
Description International Symposium: The implications and impacts of a responsibility agenda for synthetic biology, September 2018. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Title: 'The implications and impacts of a responsibility agenda for synthetic biology'.
This international interdisciplinary symposium provided an important opportunity to explore and debate the implications of different models of (responsible innovation/ responsible research and innovation (RI/RRI) for a range of interested parties. The symposium brought together leading social and scientific researchers, regulators, policy advisors, and other stakeholders to discuss the scientific, social, ethical, legal and regulatory issues raised by the burgeoning development of synthetic biology.
We were joined by colleagues from a range of disciplines (including science and technology studies, biochemistry, microbial genetics, biology, computer science, synthetic biology, history, law, ethics, philosophy, politics, sociology), from a range of jurisdictions and cultural experiences (including the Netherlands, Hungary, Italy, and the UK) and from a range of policy and practice backgrounds to assist these deliberations. The symposium ran over two days and included presentations and round-table discussion. Each session was chaired by either project participant or external guest.
Year(s) Of Engagement Activity 2018
 
Description Museum based public engagement 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact a series of 6 'pop-up' interventions ate the Great North Museum Newcastle. Activities aimed at parents and children visiting the museum with hands-on activities to engage families with an aspects of synthetic biology. The PDRA was assisted by three students from Newcastle University's Museum, Galleries and Heritage Masters courses, who collated basic information about the visitors and their interest in the 'pop/up'. The team interacted with 399 visitors (including 240 children), completing activities such as making a clock or an origami butterfly. Jigsaw puzzles were made for smaller children.
All activities aimed to start conversations about aspects of synthetic biology; such as the possible uses of a circadian clock from cyanobacteria or the research being done on DNA and RNA origami nanostructures.
Year(s) Of Engagement Activity 2019
URL https://www.ncl.ac.uk/peals/news/item/spp.html
 
Description Participation in creation of the art exhibition in Hancock Museum based on Portabolomics research project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The exhibition challenged the public view on synthetic biology and made people think in terms of the future role of research in sustainable economy
Year(s) Of Engagement Activity 2020
 
Description museum exhibition and short film 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This is a small exhibition of original work created by artist Marianne Wilde and including a short 'art' film about synthetic biology. It is place within the Great North Museum Newcastle and will be open until Summer 2020.
Year(s) Of Engagement Activity 2020