ORNL teams receive funding through DOE BRaVE initiative to study biopreparedness

(Press-News.org) The Department of Energy’s Office of Science has selected three Oak Ridge National Laboratory research teams to receive funding through DOE’s new Biopreparedness Research Virtual Environment, or BRaVE, initiative.

BRaVE, announced earlier this year, aims to build on biopreparedness research that delivered high-impact results in the fight against COVID-19. In the height of the pandemic, DOE national laboratory scientists combined fields such as biology, high-performance computing and manufacturing to bolster the national supply of personal protective equipment and improve virus testing and treatment.

“The advances made in this program will revolutionize our understanding of the science underlying a range of potential biological events and transform the nation’s ability to prepare for, and respond to, future biological threats,” said Asmeret Asefaw Berhe, Director of the DOE’s Office of Science. “Further, these advances will complement research efforts associated with other federal agencies and will be broadly applicable to understanding plant pathogens of crops that are central to DOE’s bioenergy program, as well as other biological systems.”    

The initiative encourages continued collaboration across disciplines to bolster DOE’s strategy for general biopreparedness and response to biological threats. BRaVE will provide $105 million in funding across three years to support research in five focus areas.

“ORNL’s expertise and facilities provided an invaluable resource to the fight against COVID. We are thrilled to have an opportunity to lead three new projects, each composed of multidisciplinary, multi-institutional teams, that will address complex biopreparedness challenges,” said ORNL Deputy for Science and Technology Susan Hubbard. “The new projects will take advantage of the Office of Science user facilities at ORNL — the Spallation Neutron Source, the High Flux Isotope Reactor, the Center for Nanophase Materials Sciences and the Oak Ridge Leadership Computing Facility — to advance BRaVE frontiers.”

The three ORNL researchers and their teams receiving BRaVE funding are:

Heidi Hanson, group leader of the Biostatistics and Biomedical Informatics group, will lead a research team for the proposal “Data-Driven Population Health Surveillance at Scale for Pandemic readiness” in the focus area “Elucidate Multiscale Ecosystem Complexities for Robust Epidemiological Modeling.”

U.S. health data collection is largely siloed in health care institutions, making it difficult for scientists to understand disease trends. In this project, Hanson and her team will develop a large-scale epidemiological data collection tool for integrating near real-time disease information into agent-based models for biothreat scenarios.

“Understanding underlying propensities for morbidity and mortality when exposed to a previously unseen biologic agent requires large amounts of health data from a diverse population. Most data in the U.S. is siloed at single institutions, limiting our ability to make inferences at the population level,” Hanson said.

During a biothreat scenario, the envisioned tools could be used to synthesize data across multiple medical records systems and rapidly identify vulnerable populations. Researchers could then dynamically simulate health outcomes with agent-based modeling for applications such as morbidity and mortality forecasting, health care capacity planning and health care resource allocation at the national level.

The research team includes ORNL’s John Gounley, Robert Bridges, Maggie Davis, Zachary Fox, Adam Spannaus, Mayanka Chandra Shekar, Chris Stanley, Guannan Zhang, Sudip Seal and James Nutaro; Argonne National Laboratory’s Rick Stevens and Thomas Brettin; and Los Alamos National Laboratory’s Jamal Mohd-Yusof and Cristina Garcia-Cardona. The research will be conducted in collaboration with the University of Southern California, Morehouse School of Medicine, Duke University, the University of Utah and the University of Arizona. 

Dean Myles, a distinguished research staff member in the Neutron Scattering Division, will lead a research team for the proposal “Accelerating Discovery Using DNP-enhanced Neutron Protein Crystallography” in the focus area “Advance Innovations in User Facility Instrumentation, Experimental Techniques, and Data Analytics.”

Neutron diffraction analysis is a highly efficient way to analyze biological systems, but most viral proteins are not compatible with this method. To overcome this hurdle and meet a need for small-molecule drug therapeutics development, Myles and his team have designed a dynamic nuclear polarization diffractometer that enhances neutron analyses to rapidly collect data from any protein, enabling faster therapeutic drug development.

The diffractometer, designed for the High Flux Isotope Reactor’s IMAGINE beamline, increases signals from hydrogen atoms, making key features in protein structures more visible for efficient characterization. The instrument reduces previous sample size requirements by a factor of 100.

“We’ll open the technique and the capability up to a much, much larger structural biology community and be able to do experiments that are currently just beyond our limits,” Myles said.

BRaVE will fund the diffractometer, 50 new-generation neutron detectors and a virtual instrument to simulate experiments with the Oak Ridge Leadership Computing Facility’s Summit and Frontier supercomputers.

The research team includes ORNL’s Huibo Cao, Lowell Crow, Dominic Giuliano, Jens Glaser, Amy Jones, Andrii Kovalevskyi, Matthew Loyd, Addi Thakur Malviya, Marshall McDonnell, Zach Morgan, Hugh O’Neill, Josh Pierce, Feiyi Wang and Guannan Zhang; ORNL-North Carolina State University’s joint faculty Flora Meilleur; Meharry Medical College’s Jamaine Davis; Fisk University’s Steven Damo; SLAC National Accelerator Laboratory’s Aina Cohen; and Argonne National Laboratory’s Andrzej Joachimiak.

Scott Retterer, a distinguished staff scientist at the Center for Nanophase Materials Sciences, will lead a research team for the proposal “Structure-guided Design of Materials to Optimize the Abiotic-Biotic Material Interface” in the focus area “Realize Understanding to Accelerate Design, Discovery, and Manufacturing of Materials.”

Scientists lack understanding about how potential pathogens interact with materials, which can lead to confusion about disease safety protocols. Retterer’s proposal aims to define the abiotic-biotic interface between materials and biological entities with the development of a multi-disciplinary workflow.

“This is all about understanding the fundamental physical and chemical interactions that occur when a pathogen like a virus, a fungus or a bacterium encounters a surface,” Retterer said. “We want to understand the cascade of physical, biological and chemical changes that occur downstream.”

The team will develop finely tuned material surfaces and employ advanced characterization tools to observe real-time interface changes while collecting biological samples and snapshots of the structure. To connect various length and time scales, researchers will use artificial intelligence and molecular dynamics modeling.

Retterer hopes to provide insights into how researchers can improve materials critical to pandemic response and develop best practices for handling sensitive biological samples during multi-institution collaborations.

The research team includes ORNL’s Rigoberto Advincula, Jack Cahill, Jan-Michael Carrillo, Liam Collins, Ben Doughty, Panchapakesan Ganesh, Rajeev Kumar, Jennifer Morrell-Falvey, Debangshu Mukherjee, Bobby Sumpter, Rama K. Vasudevan, Hanyu Wang and Alexis Williams; North Carolina Agricultural and Technical State University’s Shyam Aravamudhan, Kristen Dellinger and Leonard L. Williams; Stony Brook University’s Maya Endoh and Tad Koga; and the University of Tennessee Health Science Center’s Elizabeth Fitzpatrick.

UT-Battelle manages ORNL for DOE’s Office of Science, the single largest supporter of basic research in the physical sciences in the United States. The Office of Science is working to address some of the most pressing challenges of our time. For more information, please visit energy.gov/science. — Alexandra DeMarco

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