Research at the intersection of biology and engineering has expanded our understanding of living systems and the many unique and valuable capabilities they possess. Scientists and engineers have now begun to harness this knowledge in new ways to address some of humanity's most pressing challenges. For example, using engineered biosystems we can create innovative healthcare solutions, enable more sustainable forms of agriculture, and support clean manufacturing methods. The emerging field of Engineering Biology aims to harness biology to build technologies for a healthy, sustainable, and equitable future. However, to date the lack of a rigorous biological engineering process has resulted in biosystems that are fragile, unpredictable, and difficult to scale when applied in real-world settings. Early pioneers in fields ranging from Aerospace to Information Technologies faced similar challenges when attempting to create robust and reliable systems. Such difficulties were oftentimes overcome using methods from systems and control engineering, which enabled rigorous approaches to the design, optimisation, and realisation of engineered systems, ultimately leading to dramatic economic growth and the creation of entirely new industries. To achieve an equivalent step-change in the engineering of reliable and robust biological systems, our programme will develop similar control and Artificial Intelligence systems in biotechnology - which we term feedback biocontrollers. These biocontrollers will be designed to operate within cells, between cells, and even to interact with non-biological entities (such as computers), thereby allowing researchers and innovators to efficiently and safely harness engineered biology in its many real-world applications. The robust engineering of biological control systems will be underpinned by the development of four "Engineering Pillars". These cover Theory (mathematical/AI approaches based on systems and control theory to model, design, analyse, and optimise biosystems), Software (computational tools able to translate this theory into conceptual designs), Wetware (experimental methods and biological parts to make designs a biological reality), and Hardware (to comprehensively test, scale-up, and deploy engineered biosystems). Each Pillar feeds directly into an integrated "Design-Build-Test-Learn" cycle rooted in systems and control engineering methods, which will accelerate academic and industrial development of new biotechnologies. Technologies developed in each Engineering Pillar will be integrated to address outstanding problems in three "Grand Challenge'' application domains: Biomedicine, Agriculture, and the Environment. Our team will work with industrial partners to generate world-leading solutions for each of these areas, demonstrating how biocontrollers can revolutionise scale-up and deployment of reliable engineered biotechnologies. The EEBio programme represents a timely investment in the new field of Engineering Biology which is set to play a defining role in the future of our society and the rapidly growing Bioeconomy. Our team of world-leading experts and up-and-coming early career researchers will create tools and technologies that are key to the effective engineering of biological systems - as observed in other, mature engineering fields - but which are not yet realised for Engineering Biology. EEBio brings together recent momentum across our team for rapid impact, while also supporting development of seminal ideas; in the near-term this will help address Grand Challenges we face today, while in the long-term it will provide the foundation for many bio-based solutions that will improve human life, agriculture, and the environment. Our work will accelerate responsible industrial exploitation, open up the field to other research communities (in the life, medical and social sciences), and support public confidence in the safety and reliability of Engineering Biology.

Microbial communities are groupings of co-living organisms that perform important roles throughout nature. For example, communities of microbes live on the roots of plants, helping to support their growth, and they also inhabit the human gut, forming part of the microbiome that is fundamental to our health. Communities are highly versatile - they have evolved to thrive in many natural environments, and their members often interact to create systems in which the "whole is greater than the sum of its parts." Consequently, microbial communities are recognised as having a key part to play in the future of biotechnological research and development. However, scientists and engineers have yet to take advantage of the great potential of microbial communities. A major obstacle they face is the lack of specialised technologies to help them measure, manipulate, and control communities - this makes them difficult to study in the laboratory, or exploit in their many applications beyond. The work described in this project will address this challenge by developing first-of-their-kind control algorithms and integrated experimental technologies, designed specifically to unlock the diverse capabilities of microbial communities. This will include the creation of sensor packages that allow individual species within a community to be distinguished (without being removed or disturbed); implementation of robotic hardware for actuating changes in the community's chemical or spatial environment; and control algorithms that link sensors and actuators with mathematical models to regulate community behaviour. The capabilities of these innovative control technologies will be demonstrated in biological applications including regulating the make-up of engineered communities over time, optimising community-based biomanufacturing processes, and stabilising competition within a community by dynamically regulating mixing between its members. Each of these applications will apply control engineering in new ways to further our ability to study and manipulate complex, networked biological systems. The impact of the project will be amplified in work with industry partners, who will collaborate to deploy community control techniques in industrial bioprocesses, and support rapid and accessible dissemination of the developed technologies - accelerating their uptake across the UK's multi-billion pound Bioeconomy. Ultimately, the control technologies developed in this project will transform the ability of scientists and engineers to study and work with microbial communities. This will help realise the potential of microbial biotechnologies to address some of our century's most pressing challenges in areas ranging from clean growth to climate change to health care.