Synthetic Biology is the underpinning discipline for advances in the UK bioeconomy, a sector currently worth ~£200Bn GVA globally. It is a technology base that is revolutionising methods of working in the biotechnology sector and has been the subject of important Government Roadmaps and supported by significant UKRI investments through the Synthetic Biology for Growth programme. This is now leading to a vibrant translational landscape with many start-ups taking advantage of the rapidly evolving technology landscape and traditional industries seeking to embed new working practices. We have sought evidence from key industry leaders within the emerging technology space and received a clear and consistent response that there is a significant deficit of suitably trained PhDs that can bridge the gap between biological understanding and data science. Our vision is a CDT with an integrative training programme that covers experimentation, coding, data science and entrepreneurship applied to the design, realisation and optimisation of novel biological systems for diverse applications: BioDesign Engineers. It directly addresses the priority area 'Engineering for the Bioeconomy' and has the potential to underpin growth across many sectors of the bioeconomy including pharmaceutical, healthcare, chemical, energy, and food. This CDT will bring together three world-leading academic institutions, Imperial College London (Imperial), University of Manchester (UoM) and University College London (UCL) with a wide portfolio of industrial partners to create an integrated approach to training the next generation of visionary BioDesign Engineers. Our CDT will focus on providing an optimal training environment together with a rigorous interdisciplinary program of cohort-based training and research, so that students are equipped to address complex questions at the cutting edge of the field. It will provide the highly-skilled workforce required by this emerging industry and establish a network of future UK Bioindustry leaders. The joint location of the CDT in London and Manchester will provide a strong dynamic link between the SE England biotech cluster and the Northern Powerhouse. Our vision, which brings together a BioDesign perspective with Engineering expertise, can only be delivered by an outstanding and proven grouping of internationally renowned researchers. We have a supervisor pool of 66 world class researchers that span the associated disciplines and have a demonstrated commitment to interdisciplinary research and training. Furthermore, students will work directly with the London and Manchester DNA Foundries, embedding the next generation bioscience technologies and automation in their training and working practices. Cohort training will be delivered through a common first year MRes at Imperial College London, with students following a 3-month taught programme and a 9-month research project at one of the 3 participating institutions. Cohort and industry stakeholder engagement will be ensured through bespoke training and CDT activities that will take place every 6 months during the entire 4-year span of the programme and include multi-year group hackathons, training in responsible research and innovation, PhD research symposia, industry research days, and entrepreneurial skills training. Through this ambitious cohort-based training, we will deliver PhD-level BioDesign Engineers that can bridge the gap between rigorous engineering, efficient model-based design, in-depth cellular and biomolecular knowledge, high throughput automation and data science for the realisation and exploitation of engineered biological systems. This unique cohort-based training platform will create the next generation of visionaries and leaders needed to accelerate growth of the UK bioeconomy.

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.