Leal contributes to multi-institution precision phage platform effort

Researchers from the Carl R. Woese Institute for Genomic Biology will partner with investigators from industrial and academic institutions, including Ginkgo Bioworks, Baylor University, University of Minnesota, Oregon State University, and Oregon Health & Science University, on a five-year initiative funded by the Advanced Research Projects Agency for Health and overseen by Program Manager Andrew Brack, PhD.

The project, “Microbe/phage Investigation for Generalized Health TherapY (MIGHTY),” aims to harness the natural predators of bacteria – known as phages – as precision tools to shape the human microbiome and promote health. “We are very excited to be hosting this project at the IGB,” said IGB Director Gene Robinson, “The new ARPA-H agency aims to fund creative, transformative ‘moonshot’ initiatives, and the MIGHTY project more than fits the bill. We look forward to the transformative research that this contract will enable.”

Our bodies contain trillions of bacteria that can influence our health. Many are beneficial, but disruptions in their numbers or invasion by pathogens can cause a variety of diseases. For decades, antibiotics have been our go-to defense against harmful bacteria, but they also indiscriminately kill the natural bacterial residents of the microbiome that are important for maintaining health. This often leads to microbiome imbalances, or dysbiosis, that can fuel chronic diseases. Meanwhile, antibiotic resistance continues to rise, compounding the global public health crisis.

A Precision Alternative to Antibiotics

Currently, there are few reliable tools that can restore the microbiome balance. Researchers are now turning to phages, the naturally occurring viruses that selectively infect and kill bacteria and already exist throughout the human body. Phages have potential transformative uses as precision antimicrobials because they target specific pathogens while leaving beneficial bacteria unharmed. However, the process of isolating phages from the environment for therapeutic purposes is currently slow and inefficient, and single-phage treatments often fail due to rapid bacterial resistance, leaving the generalized use of phages still out of reach. 

Overcoming these challenges, the MIGHTY team will create a platform that enables rapid isolation of bacteria and phages at an unprecedented scale and apply mechanistic modeling and artificial intelligence/machine learning methods to identify effective phage combinations that eradicate harmful bacteria.

Professor and Racheff Faculty Scholar Cecilia Leal of the Department of Materials Science and Engineering at The Grainger College of Engineering, University of Illinois Urbana-Champaign, will contribute to this project by designing new materials optimized to encapsulate and deliver phages with strong antibacterial activity to the oral cavity. 

"I am excited to join the highly interdisciplinary MIGHTY team in pioneering a generalizable and scalable platform technology for controlling bacteria in a variety of contexts," Leal said. "I am very motivated to work on this project because realizing the full potential of antibacterial organisms hinges on our ability to design materials that can effectively formulate and deliver them precisely where they are needed."

Starting with Oral Health – And Reaching Further

As an initial application, the team will focus on the oral microbiome where bacterial pathogens drive tooth decay and gum disease, and also contribute to chronic illnesses, including cardiovascular disease, Type II diabetes, and oral and colorectal cancers. The researchers aim to develop an easy-to-use, low-cost phage product – such as a chewable gummy – that can improve oral health for everyone.

“Our long-term goal is to usher phage-based therapeutics into mainstream medicine as routine and widely accessible treatments,” said Asma Hatoum-Aslan, an associate professor of microbiology and lead on the project. “A simple product for oral care is just the start – this platform will support solutions for gut, metabolic, and autoimmune diseases as well.”

The team will leverage researchers’ deep expertise in bacterial genetics, phage biology, microbiome studies, computational biology, and machine learning, and integrate cutting-edge technologies, such as Ginkgo’s ultra-high-throughput screening technology, and activity-based chemical probes developed at Baylor. 

"Collaborating with Ginkgo Bioworks and our academic partners brings a new dimension to our research,” said Cari Vanderpool, Department Head and McKnight Presidential Endowed Professor of Plant and Microbial Biology at the University of Minnesota, and co-investigator on the project. “Together, we're poised to develop innovative treatments that could fundamentally improve health by targeting the microbiome in precise and sustainable ways."

Illinois Grainger Engineering Affiliations 

Cecilia Leal is an Illinois Grainger Engineering professor of materials science and engineering and is affiliated with the Department of Bioengineering and the Carle Illinois College of Medicine. She holds the Racheff Faculty Scholar appointment.