BU Researchers Awarded Grants to Develop Antiviral Treatments against Henipaviruses
Rachel Fearns, PhD and Elke Mühlberger, PhD, both professors of microbiology at Boston University Chobanian & Avedisian School of Medicine, each have been awarded three-year grants from the Bill & Melinda Gates Foundation to study henipaviruses – bat-borne viruses that cause severe and often fatal illness in humans and have the potential to emerge as a pandemic threat. Fearns and Mühlberger are both investigators at the Boston University National Emerging Infectious Diseases Laboratories (NEIDL), a state-of-the-art center with a mission to characterize emerging pathogens and work towards developing countermeasures against them.
Fearns, who received $2.26 million, will work with collaborators, Jonathan Abraham, MD, PhD from Harvard Medical School and Margaret Stratton, PhD from the University of Massachusetts/Amherst and their research groups to characterize the structures and functional properties of a henipavirus polymerase. The polymerase is essential for the virus to propagate and is a good target for antiviral drug development. By characterizing the polymerase in different functional states, the team plans to identify features that are essential for it to make movements necessary for it to perform its functions. This research will open the door to developing antiviral treatments.
Fearns’ research focuses on the transcriptional and genome replication mechanisms of a variety of non-segmented negative strand RNA viruses, the group of viruses to which henipaviruses belong. This group of viruses contains several significant human pathogens, including respiratory syncytial virus (RSV), human metapneumovirus, measles, mumps, and parainfluenza viruses, and emerging highly pathogenic viruses, such as Nipah, Marburg and Ebola viruses. Her goal is to understand the processes of transcription and genome replication, both at a molecular level and within the context of the cellular environment to identify targets for drug development.
Mühlberger received $3 million for a highly collaborative project that focuses on the use of human-relevant infection models to study henipavirus pathogenesis. The BU team combines expertise in studying BSL-4 viruses (Mühlberger), generating human iPSC-derived cells and organoids (Darrell Kotton, MD, David C. Seldin Professor of Medicine; Gustavo Mostoslavsky, MD, PhD, professor of medicine & microbiology), using humanized mouse models to study viral infections (Florian Douam, PhD, assistant professor of microbiology), cutting-edge histopathology approaches (Nicholas Crossland, DVM, DACVP, assistant professor of pathology and laboratory medicine), and computational modeling (Stefan Wuchty, PhD, associate professor at the Center for Computational Science, University of Miami). The team will collect and analyze transcriptional data from the various infection models to identify biomarkers and potential drug targets against henipavirus infections in the specific tissues and cell types.
Mühlberger has a long-standing research interest in studying highly pathogenic viruses that cause severe disease in humans with high case fatality rates. This includes Ebola virus and other viruses that must be handled at the highest biosafety level. Her lab studies different aspects of the viral infection cycle with a focus on identifying determinants of virulence.