Transformative solutions to antibiotic resistance

How the University of Oxford is helping to lead the fight against one of the greatest global health challenges

More than 1.2 million people die each year as a direct result of antibiotic-resistant bacterial infections. But this number could soon rise dramatically: as resistance spreads, an increasing number of infections are becoming harder – and sometimes impossible – to treat as antibiotics become less effective.

‘Antibiotic resistance is already a major challenge and one that is growing fast. Without effective action, we could soon be in a “post-antibiotic era”, where even minor cuts and common infections could be fatal, and standard medical procedures become highly risky,’ said Harrison Steel, Associate Professor of Engineering Science at the University of Oxford.

To address this threat, in September 2023 President Biden announced a new Defeating Antibiotic Resistance through Transformative Solutions (DARTS) project. Backed by up to $104 million of funding, it is the largest investment made to date by the USA’s Advanced Research Projects Agency for Health (ARPA-H).

The aim of DARTS is to combine the power of artificial intelligence (AI), high-throughput testing and robotics to develop rapid platforms to test for antibiotic resistance. Led by Harvard Medical School, DARTS brings together more than twenty partners in the United States. As the only non-US partner in the project, Professor Steel’s research group was invited to participate due to its world-leading expertise in developing robotic applications to address biological challenges.

‘Our aim is to develop a step-change technology to diagnose antibiotic resistance exponentially faster than current gold-standard methods’ he said. ‘When a patient arrives at a hospital with a bloodstream infection, every minute matters and so choosing the correct antibiotic quickly is crucial to success. However, methods currently used to identify bacteria and their antibiotic susceptibility have remained largely similar for the past 50 years and are simply not up to the challenge.’

Professor Harrison Steel. A white man with short brown hair wearing a blue shirt.

Professor Harrison Steel

Professor Harrison Steel

Currently, bacteria are often tested for their susceptibility to drugs by growing colonies in the presence of different antibiotics. But these tests are slow, requiring hours or even days to understand how resistant bacteria are to a range of antibiotics.

‘This means that clinicians often have to essentially guess which antibiotic may be effective based on their experience, or prescribe a broad cocktail that may be effective against multiple bacterial infections,’ said Professor Steel. ‘On the one hand, you risk prescribing an ineffective antibiotic, and on the other you risk fuelling further resistance to antibiotics in the community.’

'We were excited to expand our work with the team at the University of Oxford as our project's international partner. They have a unique track record creating robotics to solve outstanding problems in biosciences, and we are excited to apply this together to tackle the threat of antibiotic resistance.’
Professor Johan Paulsson from Harvard Medical School
rod-like bacterial cells with a flourescent glow. There is a colour change from green to blue

A transformative solution

DARTS will combine the power of artificial intelligence, high-throughput testing and robotics to develop a step-change technology to diagnose antibiotic resistance.

To address the current issues with detecting AMR, the DARTS project envisions ultra-high-throughput imaging and culturing platforms that can continuously and automatically track thousands of bacterial samples, probing how they might evolve over long periods of time in response to antibiotics. By collecting data across many experiments performed in the laboratory, advanced AI algorithms could then predict possible outcomes of treatments, and in doing so help inform clinical decisions.

A hand wearing a blue latex glove reaches down to pick up a petri dish with mould growing on agar. There are other similar petri dishes on the table.

‘Based on our long experience of developing bioreactors and other robotic tools we have the capabilities necessary to build technologies that can fast-forward standard testing approaches’ said Professor Steel.

‘We propose a system where samples are cultured in controlled environments which can accelerate growth of cells isolated from patients. This would enable different hypothetical scenarios to be tested in real-time, returning meaningful results within an hour. When done on a high-throughput scale, this would allow multiple drugs and different combinations to be tested in parallel.’

A dark rectangular strip with fluorescent vertical strips across the top and bottom. These strips represent individual fluorescent bacteria confined within vertical channels of a microfluidic "chip" waiting to be screened.

Image shows individual fluorescent bacteria confined within vertical channels of a microfluidic "chip" waiting to be screened. The image was taken using a microscope built by the Steel research group.

Image shows individual fluorescent bacteria confined within vertical channels of a microfluidic "chip" waiting to be screened. The image was taken using a microscope built by the Steel research group.

Besides removing the guesswork in treating patients with life-threatening infections, such a tool would supercharge the search for new effective antibiotics while helping scientists to understand how different clinical conditions and practices impact the emergence and spread of resistance.

But developing these platforms will require engineering ambitious new microscopy hardware and high-throughput analysis software. Dr Idris Kempf, a Postdoctoral Researcher in Professor Steel's research group working on control algorithms, explains: ‘The goal of the DARTS project is to develop tools to analyse and influence the behaviour of individual bacterium, contrasting existing state-of-the-art technology that mainly allows characterising the average behaviour of a population of millions,’ he says.

‘With our new technology, we will continuously measure the activity of each bacterium and, based on these measurements, automatically make decisions on the subsequent actions to be taken, for instance exposing the bacteria to external stimuli for drug screening. The software that controls these processes will use novel AI-based technology to track the bacteria on microscope images, similar to what is used in self-driving cars, and deep learning to characterise the behaviour of bacteria in real time, such as the development of antibiotic resistances.’

‘The DARTS project provides a unique opportunity for me to engage in a broad, international collaboration focused on addressing critical issues related to antibiotic resistance. I hope that this project will help to bridge the large gap between engineering and biology, and contribute to the growth of the engineering biology community.'
Dr Idris Kempf
Dr Idris Kempf: a young man wearing glasses and a purple shirt. He stands in front of a stone wall with rooftops and buildings in the background.

Dr Idris Kempf.

Dr Idris Kempf.

A ‘rising star’ in engineering

Professor Harrison Steel in 2020, working in his laboratory. He works on a metal box-like structure with many wires and components.

Image shows Dr Harrison Steel working on the OxVent Ventilator project in 2020.

Image shows Dr Harrison Steel working on the OxVent Ventilator project in 2020.

The Steel Lab’s participation in DARTS reflects their international reputation for working at the interface between robotic technologies and synthetic biology to design biologically-inspired solutions to scientific, environmental, and industrial challenges.

In 2019 Professor Steel founded the Bioreactor platform venture Chi.Bio to disseminate an automated robotic system for biotechnological research and development as an open-source, low-cost technology. The platform is now widely used in academic and industrial laboratories worldwide, particularly benefiting those in developing countries who have more limited access to advanced analytical equipment.

Professor Steel is also a science advisor to several start-ups in areas that include biomanufacturing, environmental remediation, and new biomedical therapeutics. During the coronavirus pandemic, he played a leading role in the OxVent ventilator project and work to develop rapid testing for COVID-19. Having only completed his DPhil in 2019, Professor Steel has been identified as a ‘rising star’: in 2022, he was awarded a £100,000 Philip Leverhulme prize, and in 2023, he was named Young Engineer of the Year by the Royal Academy of Engineering.

The Chi.Bio Bioreactor platform, a rectangular metal box with a small screen and USB ports

The Chi.Bio Bioreactor platform developed by Dr Harrison Steel during his D.Phil working with Professor Antonis Papachristodoulou in the Department of Engineering Science. Since its development, the platform has gone on to be used by over 100 research groups and start-up companies in Biotechnology around the world.

The Chi.Bio Bioreactor platform developed by Dr Harrison Steel during his D.Phil working with Professor Antonis Papachristodoulou in the Department of Engineering Science. Since its development, the platform has gone on to be used by over 100 research groups and start-up companies in Biotechnology around the world.

A new generation of interdisciplinary engineers

Besides developing critically-needed technologies, the project will also play a key role in training the next generation of interdisciplinary engineers.

Marco Corrao, a second year DPhil student in Professor Steel's research group, is working on the control and robotic systems needed for an automated laboratory platform for accelerated bacterial evolution. ‘Working on such an interdisciplinary project at the interface of automation, mathematics and biology really pushes all of us to think beyond our specialties, fosters collaboration, and encourages the exchange of ideas’ he says.

‘These are incredibly valuable skills to have as a modern bioscience researcher. It is also exciting to see our work contributing towards a goal that has such a high value to society, since antibiotic resistance has been recognised as one of the leading public health threats of the 21st century.’

‘Being involved with the DARTS project has been a brilliant experience so far. A recent highlight was to meet our project collaborators in Boston, where I also had the chance to present my work at the International Workshop on Bio-Design Automation. It was a great opportunity to meet other young researchers working at the frontier of bio-design automation, and to learn about some exciting directions towards which synthetic biology is moving.’

six researchers wearing lab coats sit at benches in a laboratory. Some are working at computer screens, others are carrying out experiments.

At work in the Steel laboratory

At work in the Steel laboratory

 ‘A high-throughput automated platform for microbial evolution will enable us to investigate how antibiotic resistance emerges at the molecular level, which can ultimately inform the development of novel antibiotics'

Marco Corrao, second year DPhil student

Marco Corrao, a young man with short brown hair wearing a dark blue jumper. He stands in an open plan office building.

'The Steel research group is a very stimulating place to work. Having previously worked in labs that were heavily biology-focused, it is very exciting to work on a project that combines a range of disciplines, including biology, engineering, programming and control theory.’

Jessica James, second year DPhil student

Jessica James, a young lady with shoulder length blonde hair wearing a beige jumper and a pendant. She stands in front of a plain black background

According to Professor Steel, his research group has grown into a very diverse community, including wet lab biologists, robotic engineers, and control theorists. 'This enables us to tackle problems with a combinatorial approach that includes theoretical analysis, experimentation, and application-focused engineering,' he says. 'We are also fortunate at Oxford to be able to collaborate with many other excellent academic groups, besides the University’s various industrial partners.'

‘Since setting up our research group in 2020 it has been very rewarding to see the team grow in diversity and expertise' he adds. 'I am proud of how far we have come in taking blue-sky fundamental research and translating it to applications across biotechnology, control engineering, and beyond. AMR is one of the outstanding medical challenges of our time. I hope that with increasing international cooperation in this area we will be able to work together to build solutions – and do so more rapidly than the bacteria can create new challenges for us!’

A young man in a laboratory wearing a lab coat works on a complex piece of equipment with many tubes and wires

Marco Corrao at work in the lab

Marco Corrao at work in the lab

More on antibiotic and antimicrobial resistance research at Oxford:

Learn about the work of The Ineos Oxford Institute for antimicrobial research

Find out about The Global Research on Antimicrobial Resistance (GRAM) Project

Discover the work of The Oxford Martin Programme on Antimicrobial Resistance Testing