Building a COMPASS to navigate future pandemics

Viruses like SARS-CoV-2 don’t respect boundaries, moving between species and continents and leaving destruction as they go. Beating the next pathogen with pandemic potential means getting good at crossing borders ourselves — between fields of study, between research universities, and between scientists and the wider community.

An $18 million grant announced by the U.S. National Science Foundation (NSF) will put that goal within reach. The award brings together five universities and more than 20 researchers, academics, and public health experts to establish the Virginia Tech-led Center for Community Empowering Pandemic Prediction and Prevention from Atoms to Societies (COMPASS).

Headquartered in the university’s interdisciplinary Data and Decision Sciences Building, the center’s collaborators will have access to high-tech labs, data centers, and other facilities. But the work won’t be confined to the buildings or even the borders of Virginia Tech.

Cornell University, the University of Michigan, Meharry Medical College, and Wake Forest University also will collaborate to meet the critical challenge of thwarting infectious diseases that threaten the global community. T.M. Murali, associate department head for research in the Department of Computer Science will direct the new center.

The COMPASS Center is part of an overall $72 million NSF Predictive Intelligence for Pandemic Prevention program established to better understand how pathogens and diseases emerge and spread as well as to train the next generation of scientists to carry on the work to stop them. The project was supported by two rounds of funding from the Office of the Executive Vice President and Provost that established a Virginia Tech research thrust for pandemic prediction and prevention.

“This NSF award exemplifies what can be achieved by convening an interdisciplinary team of faculty committed to advancing an area of particular strength at Virginia Tech – the development of predictive models and approaches necessary for management of infectious diseases that so often arise from the inextricable linkages between humans, animals, and the environment,” said Executive Vice President and Provost Cyril Clarke. “Pandemic prediction and prevention is an area of scholarly emphasis selected for prioritized investment through our transdisciplinary Destination Area program.”

At a glance

The $18 million Virginia Tech led COMPASS Center will

• Bring together researchers and academics from many disciplines and rally them to one focus: understanding how a virus infects its host and what it does in the body
• Include researchers from Cornell University, the University of Michigan, Meharry Medical College, and Wake Forest University
• Focus on talking with, and more importantly, listening to the needs and concerns of the public
• Inspire and train the next generation of scientists to further pandemic science and better connect with non-scientists about it

The interdisciplinary COMPASS Center established under an $18 million National Science Foundation grant includes more than 20 collaborators across five institutions. Some of the Virginia Tech researchers and staff involved are: (top row, from left) Padma Rajagopalan, X.J. Meng, Patricia Raun, Lisa Lee, and T.M. Murali and (bottom row, from left) Leslie Thornton-O’Brien, Kylene Kehn-Hall, and Anuj Karpatne. Photo by Tonia Moxley for Virginia Tech.

The majority of emerging human viruses originate from wildlife and domestic animal species. “There are many challenges in trying to determine if a virus that currently infects one or more animals can jump to humans, and when that leap can lead to a pandemic,” Murali said. 

The center will focus on answering four key questions:

• How does a pathogen, like a virus, jump from one species to another? Researchers will use predictive models based on machine learning to find out how changes in a pathogen may enable it to infect new species.
• How does a pathogen replicate inside a host? The research group will develop new ways to create  organoids — miniaturized models of organs that mimic their key functions — to grow a new virus, study its life cycle, and test new and existing drugs and therapies on it. 
• What are the factors that permit a pathogen to persist in the environment? The goal of the researchers is to develop approaches that can identify the features of a pathogen or the environment that can cause inactivation.
• How do we empower the public with the scientific knowledge gained through this work? Faculty and students involved in COMPASS will be trained to better communicate with the public around pandemic science, and the researchers will meet with the public in community dialogues.

“What we are focusing on is really trying to understand how a pathogen or a virus can shift to a new host and how it interacts with a host at a cellular, organ, or the whole body,” Murali said. “Essentially, we want to discover the rules of life that govern these interactions and use that information to make the world safer.”

In the collaborators’ words

To achieve the ambitious goal of understanding and predicting how pathogens interact with hosts, collaborators will work in four crucial areas. 

Jumping the species barrier

X.J. Meng, University Distinguished Professor of Molecular Virology at the Virginia-Maryland College of Veterinary Medicine, studies emerging and zoonotic viruses of veterinary and human public health significance and develops life-saving vaccines. 

“With colleagues at Cornell University and the University of Michigan, we will attempt to predict, through novel machine learning systems, which viruses will jump from animals to humans, and which specific mutations within the viral genome may enable these shifts. We will also experimentally validate the computational predictions through biological studies using human organoid cultures,” Meng said. “Successful identification of genetic elements responsible for virus species jumping and adaptation will help design better prevention and control strategies against emerging viruses.”

Replicating inside a host

Padma Rajagopalan, Robert E. Hord Jr Professor in the Department of Chemical Engineering, and collaborators at the Wake Forest Medical School will bring their expertise in liver and other tissues and organs  to the collaboration. While viruses and other pathogens are the subject of much study, it can be very difficult to grow them in the lab. Organoids could be the key to unlocking a deeper understanding of the life cycle of an emerging virus and ways to counteract it.

“We believe that 3D multicellular tissue organoids — miniature tissue models that mimic key functions of an organ — can be used to understand how viruses enter, propagate, and potentially cause damage to different organs either individually or when integrated together,” Rajagopalan said. “On the other side of the equation, engineers, biologists and virologists can work together to test drugs that could be used against the virus and any complications it causes.”

Persisting in the environment

University Distinguished Professor Linsey Marr in the Charles Edward Via, Jr. Department of Civil and Environmental Engineering and collaborators at the University of Michigan will seek to discover what helps emerging pathogens grow and survive and what conditions can arrest their spread.

“How long a virus survives, or persists, in the environment is one key factor in its ability to spread rapidly. If SARS-CoV-2 didn’t survive long in respiratory droplets, we would not have had a pandemic,” Marr said. “COMPASS will help us be able to predict whether new threats, such as the H5N1 flu virus in cows, can survive for a long time in milk, or whether it would quickly die off under certain conditions.”

Empowering scientists and the public

In 2016, Alumni Distinguished Professor of Theatre Arts Patricia Raun helped found the university’s Center for Communicating Science, which she now directs. Based on a concept developed by actor and science enthusiast Alan Alda, the center uses the tools of the arts, including embodied learning, deep listening, improvisation, role play, and storytelling to train and educate everyone about science.

Raun and her staff will work with COMPASS faculty and students to teach them new ways to both talk with and listen to the public. Students receiving this training will include summer interns recruited by collaborators at Meharry Medical College.

“I believe it’s going to take all of us to solve the world’s challenging problems,” Raun said. “My part of that is around helping scientists and people in highly technical fields connect with the public and communicate with us in ways we can understand.”

The Virginia Tech faculty collaborating within the COMPASS Center include

• T. M. Murali, principal investigator and center director
• Julie Gerdes, assistant professor of technical and professional writing and rhetoric, College of Liberal Arts and Human Sciences
• Anuj Karpatne, associate professor of computer science, College of Engineering and core faculty at the Sanghani Center for Artificial Intelligence and Data Analytics
• Kylene Kehn-Hall, professor of virology in the Virginia-Maryland College of Veterinary Medicine and director of the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens
• Lisa M. Lee, interim senior associate vice president for research and innovation and director in the Division of Scholarly Integrity and Research Compliance
• Linsey Marr, University Distinguished Professor and Charles P. Lunsford Professor of Civil and Environmental Engineering
• X.J. Meng, University Distinguished Professor of Molecular Virology, Virginia-Maryland College of Veterinary Medicine and professor of internal medicine at the Virginia Tech Carilion School of Medicine
• Padma Rajagopalan, Robert E. Hord Jr Professor of Chemical Engineering and program director of the Computational Tissue Engineering Interdisciplinary Graduate Education Program
• Naren Ramakrishnan, Thomas L. Phillips Professor of Engineering and director of the Sanghani Center for Artificial Intelligence and Data Analytics
• Patricia Raun, Alumni Distinguished Professor of Theatre Arts and director of the Virginia Tech Center for Communicating Science

Next steps

One of the first events that the COMPASS Center will organize is a National Dialogue on the Ethics of Pandemic Research in Washington D.C. in November. The goal of the event is to incorporate community voices and feedback into research in pandemic science. Researchers and community-based partners will collaboratively identify key ethical questions that arise in pandemic science.

The center will collaborate on diverse research projects with industry, federal agencies, and international organizations. Murali expects these efforts to result in a robust public-private ecosystem to provide solutions to diverse problems in pandemic science.