Researcher Co-Leads Mission to Halt the Next Pandemic

Struck with a virus no one had ever seen, the scientific world scrambled to identify and understand SARS-CoV-2 in 2020, racing against the clock but slowed by a disconnected research environment.

Work today by the Biopreparedness Research Virtual Environment (BRaVE) initiative, backed by $112 million from the U.S. Department of Energy, is aimed at preventing that scenario from happening again.

David Pollock, PhD, professor of biochemistry and molecular genetics at the University of Colorado School of Medicine, is co-lead researcher on a $10.8 million multi-institutional Northwest BRaVE project, coordinated by the Pacific Northwest National Laboratory. Their aim is to put structure, proteomic, metabolomic and evolutionary genomic information at scientists’ fingertips, along with a model system in place to help them understand how pathogens spread and coevolve before the next emerging pathogen hits pandemic levels.

Data-flow repository

Pollock describes the information repository at the center of the project as a “Google Earth”-type platform that allows researchers across “-omics” fields to nimbly collect and share data. Rapid access to large, integrated datasets – generally missing at the start of the COVID pandemic – allows scientists to speed experimental integration and share discoveries that could halt a pathogen’s spread.

“Part of what we’re doing is called federated data,” Pollock said. “The system allows you to see all the data and pull down and organize datasets as needed from this one site. And you’re doing that without having to log into 20 different sites and figure out all their systems … People tend to get into their own silos. But with a system like this, even though scientists have done their own research, we’re making sure the data can easily flow in all directions.”

Modeling pathogenic evolution

In addition to developing the repository, Pollock’s team is creating a model system to study virus-host interactions using cyanobacteria, the bulk of which live in the oceans and account for up to 50% of Earth’s photosynthesis, and their parasitic cyanophages. They are focusing on how convergence and coevolutionary interactions take place when cyanobacteria and cyanophage move into coastal and estuary environments.

“Because they are such a ubiquitous organism, we’ve got huge opportunities to see repeated instances of convergent evolution and coevolution,” Pollock said. “Another reason we’re using them is they’re really small – on the order of 200 microns – and that’s small enough that we can do cryo-electron tomography on whole organisms.”

The cutting-edge cryo-electron tomography allows scientists to clearly see three-dimensional, molecular images of pathogens and how they interact with host cells. Scientists “used this technology during the COVID pandemic to get really nice visuals of the virus, how it binds to the cell, and the internal structures when the virus infects. So, in our system you’re seeing individual cells and what’s happening in those cells as an infection process goes on,” Pollock said.

Host shift and adaptation

Coevolution takes place when, for example, a virus undergoes a “host shift” – or moving from one organism to another.

Coevolution in the infection process involves “combinations of interactions (between molecules) that need to happen to make a more ‘fit’ or ‘advantageous’ virus, which is disadvantageous for us,” Pollock said. “During COVID, we became much more aware of how those processes were going on and were really key toward understanding the host shift and adaptation to a new host.”

In basic, molecular-level terms, the model system focused on ubiquitous organism adapting to estuaries will give scientists insights into host-pathogen interactions and how they’ve evolved. Meanwhile, on a macro level, the model and its accompanying data repository will expedite scientists’ efforts globally to head off future biothreats.

The project is getting a boost from students at Northwest Indian College. They are enhancing their scientific education by conducting in-the-field work in the coastal areas of northwest Washington state, and integrating that with learning about analysis using cutting-edge techniques at National Laboratories all the way through to using this information to address public health (with the Colorado Department of Public Health and Environment, a project collaborator).

“By having students from the college interact with the project, we’re helping build a pipeline for indigenous populations into science and health fields,” Pollock said.