By Marshall Swearingen MSU News Service

BOZEMAN – A Montana State University researcher and her colleagues have received a $5.2 million grant to push the boundaries of a new approach for treating flu and other fast-evolving viruses that resist traditional vaccines.

Connie B. Chang, assistant professor in the Department of Chemical and Biological Engineering, will receive $1.3 million of the funding, which was awarded in October by the Defense Advanced Research Projects Agency (DARPA), an independent agency of the U.S. Department of Defense that funds “high-risk, high-reward” projects.

Chang and her team will explore the use of a sophisticated method called drop-based microfluidics for producing therapeutic interfering particles, or TIPs, for treating influenza.

“Once we understand how this applies to flu, we could potentially use this method to make TIPs for other viruses,” Chang said. DARPA lists more than 40 “high priority viral pathogens,” including Ebola, HIV and Zika, as candidates for treatment using TIPs.

TIPs are stripped-down, harmless versions of viruses. While traditional vaccines consist of a weakened or killed virus that prompts the body’s immune system to produce antibodies, TIPs are engineered to hijack a harmful virus’s reproduction process, creating more TIPs while reducing the ability of the virus to spread and cause illness.

TIPs are thought to have several potential advantages over vaccines, including an ability to co-evolve with the harmful virus and remain effective for longer periods.

Microfluidics “is a powerful tool” that shows promise for producing TIPs, Chang said, because it allows researchers to cultivate millions of strains of viruses in a highly controlled environment, at lower cost and with smaller lab requirements.

“Chang’s work is helping to enable experiments, using microfluidics, that used to require entire rooms full of researchers and equipment,” said Jeff Heys, head of MSU’s Department of Chemical and Biological Engineering.

Microfluidics technology involves manipulating microscopic drops of water and oil using networks of tiny tubes etched in palm-sized plates of glass, called “chips.” A single microfluidics chip can be used to produce millions of drops per minute.
Individual host cells infected with a virus are inserted into each of the drops. As the virus multiplies and evolves independently in each of the drops, millions of new virus strains are produced, according to Chang.

“We can then screen these viruses at rates of thousands per second” to determine their genetic makeup, Chang said. The drops containing the viral strains that show promise for further adaptation into TIPs can then theoretically be rapidly sorted out, she added.

Chang, whose Soft Matter and Microfluidics Lab is part of MSU’s Center for Biofilm Engineering, played a major role in developing microfluidics as a tool for virology with funding from another DARPA grant as a postdoctoral scholar at Harvard University, before coming to MSU in 2013 and taking a tenure-track position in 2015.

“DARPA is well-known for funding the most cutting-edge research,” Heys said.

According to DARPA, the agency has played a major role in developing hand-held GPS devices, flat-screen technology and the basis of the modern Internet.

“The research is fast-paced and interdisciplinary,” said Chang, who is one of the five principal investigators on the project, which includes Christopher Brooke of University of Illinois at Urbana Champaign, Ruian Ke of North Carolina State University, Katia Koelle of Duke University and Laura Fabris of Rutgers University. The other principal investigators are experts in virology, mathematics, evolutionary biology and materials science.

“These are challenging concepts,” Chang said. “We’re aiming for something that could seem impossible. But with DARPA, they want you to try these high-risk, high-reward projects.”