Engineering Fellowships for Growth: Advanced synthetic biology measurement to enable programmable functional biomaterials

Synthetic biology accelerates the research and development of new biotechnologies by rigorously applying engineering design principles to the way we work with biological systems. The most prominent application of synthetic biology is the rational modification and redesign of living organisms like microbes for new efficient use in sectors such as energy production, biomaterials, biomedicine, drug production and food technology. Crucial to developing and applying synthetic biology is the rigorous quantification, modelling and analysis of synthetic biology designs. By using this engineering framework researchers aim to predict how engineered biological systems will operate.

Despite many successes, it is still difficult to predict how engineered cells behave when new synthetic genetic information is added to these host cells. Key to the high failure rates in forward engineering in synthetic biology is the lack of high-quality data available on parts and devices. Without a holistic dataset reporting on performance of a biological part in its host cell, it is difficult to predict how it will behave when included in complex designs. The work proposed in this project seeks to address this by developing a novel workflow to obtain a richer-dataset on thousands of different parts and devices as they are implemented in bacterial host cells. To achieve this goal, a screening workflow will be established, that for the first time incorporates in vitro prototyping, with in vivo assaying and mass-spectrometry profiling to simultaneously capture how synthetic biology device design affects gene expression, expression load and host cell health, energy and growth. Measuring these multiple parameters in parallel will greatly enrich predictive models and ideally will lead to robust in silico predictions on performance characteristics such as growth rate and mutation likelihood. In this project, modelling will be developed specifically for this task and mass spectrometry will also be introduced as a state-of-the-art measurement tool. Both are new frontiers for synthetic biology.

While this research will have a very wide impact and accelerate the many different future applications of synthetic biology, in this project it will be specifically used to tackle a high-value biomaterials application that would be unlikely to succeed without the strong engineering foundations this work provides. For this part of the project, predictions of gene expression and growth will be used to express a library of different functional proteins in engineered microbes and microbial consortia that can then be polymerised together to generate polyprotein biomaterials with programmable catalytic and material properties. For example, by combining silk proteins with lipase enzymes in biological polymers, advanced materials such as self-cleaning fabrics can be realised. While this materials work is intended as a showcase for the foundational methods developed in this project, it will no doubt lead to many future exciting applications and new industries in a rich variety of commercial, engineering and research sectors, from fashion and manufacturing to medicine.

Synthetic biology is an EPSRC priority research area where scientists apply engineering principles to modify and reconstruct biology, in order to make biological engineering a scalable, predictable and economically successful industry for the 21st century. The UK's strong record in fundamental science puts us in an enviable position to deliver the foundational tools needed to move synthetic biology from ad-hoc custom designs to an advanced engineering discipline. The key to delivering this lucrative future is the predictable and repeatable engineering of biology from parts, but without sufficient understanding and control over how parts and devices affect the cells that they are run in, many designs in synthetic biology fail unexpectedly. To accelerate the realisation and predictability of synthetic biology designs for research and industry, foundational work is needed to bridge this gap. This project is a rational plan of foundational engineering and measurement work designed to address this gap and to advance our ability to engineer biology for human needs.

The proposed research will have immediate impact in the rapidly-growing academic and industrial synthetic biology sectors as this foundational work will increase the precision of engineering capable in living cells and enable faster turnaround times from designs to working applications. The workflow for part characterisation and the holistic characterisation methodologies, developed in this project will likely be put to use at academic and industrial research labs around the world and extended to use in other industrially relevant organisms, such as yeasts and thermophiles. The implementation of novel characterisation protocols, models and the use of mass-spectrometry measurement also all represent new development of enabling technologies that will greatly benefit research and development in academic and industrial labs alike.

Industrial biotechnology will benefit greatly as the foundational work should reveal how consortia of cells can be designed to grow at similar rates, opening up a crucial new avenue for industry where specialised cells can be reliably mixed together and perform complex tasks as division of labour. This will be especially valuable in the biosynthesis of complex compounds, by consolidated or distributed metabolic manufacturing where many synthetic genes need to be expressed at the same time. Impact will also be given to the UK engineering and bioscience research communities, by promoting leadership and training in synthetic biology within this country. This will in turn lead to greater growth in commercial/industrial synthetic biology in the UK and enhanced visibility for UK start-ups and SMEs. The applied research of this project, the synthesis of advanced biomaterials, will open up a new avenue of applications in synthetic biology in UK and Europe beyond merely providing the tools to improve existing industries. Biosynthesised functional materials may become an entirely new industry and will likely have an impact on many consumer sectors as well as on medical healthcare, defence and security sectors. Applications from biomaterials will be investigated here through responsible innovation collaborations with those researching in textiles futures and in industry.

This project will also impact on educational training, teaching new skills to those employed on the project and also providing opportunities to extend the research into undergraduate teaching via research competitions such as iGEM (http://igem.org/Main_Page). The UK has had remarkable success in teaching parts-based synthetic biology, producing many world-class undergraduate projects, so investment in further research here in the UK is critical to retaining the best students in the country and building a successful UK-based biotechnology industry.