2024 Tullie and Rickey Families Spark Awards Winner
Jingru Fang, Ph.D.
“This SPARK award gave me tremendous support to pursue an original, but risky idea. There are fascinating technologies emerging everyday in the academic world, which enable novel discoveries that cannot be made otherwise. SPARK support allowed me to apply one of these technologies to investigate a hidden side of our immune response to viral infection.”
How do bats tolerate viral infections that are otherwise fatal in humans?
Funded: January 2024
Funded by: The generosity of LJI Board Director Sandor Shapery and Rebecca Shapery
I want to understand how bats carry some of the world’s most deadly viruses, such as Ebola virus, without getting sick. There is reason to think structures called “viral factories” may hold the answer. Ebola virus-infected cells look strange under the microscope. We can see that infected cells are dotted with large granules. These granules are “viral factories,” pockets of viral proteins that carve out space to replicate inside host cells. Viruses may also use viral factories to manipulate host cell defenses. I set out to use RNA imaging techniques and a cutting-edge spatial-transcriptomic method called MERFISH to study how Ebola viral factories select and traffic host cellular mRNAs to manipulate host metabolism and immune responses.
What was the goal of your SPARK project?
I want to understand how bats carry some of the world’s most deadly viruses, such as Ebola virus, without getting sick. There is reason to think structures called “viral factories” may hold the answer. Ebola virus-infected cells look strange under the microscope. We can see that infected cells are dotted with large granules. These granules are “viral factories,” pockets of viral proteins that carve out space to replicate inside host cells. Viruses may also use viral factories to manipulate host cell defenses. I set out to use RNA imaging techniques and a cutting-edge spatial-transcriptomic method called MERFISH to study how Ebola viral factories select and traffic host cellular mRNAs to manipulate host metabolism and immune responses.
SPARK Project Results
My preliminary experiments in both human and bat cells suggest that Ebola virus uses viral factories to trap molecules called cellular mRNAs. This motivated my proposal to uncover the biological identity of trapped cellular mRNA to understand the consequence of this process. I applied a spatial-transcriptomic method called MERFISH (multiplex error robust fluorescence in situ hybridization) in collaboration with Dr. Gene Yeo’s group at UC San Diego to quantify the subcellular redistribution of over one hundred cellular mRNAs in Ebola viral factories within human kidney cells under normal versus IFN-stimulated conditions. I found that viral factories can enhance the stability of selective cellular mRNA with distinct molecular features, especially for mRNAs encoded by IFN-stimulated genes. As inflammation-related mRNAs are kept longer than they should be in cells, this will lead to unwanted systemic inflammation and pathological damage seen in Ebola virus disease.
What's next for this project?
The discovery that Ebola virus traps and enhances the stability of immune-related mRNA in viral factories is totally unexpected. This finding provides a mechanistic foundation for using type 1 IFN to resolve disease symptoms induced by Ebola virus infection. Going forward, I plan to investigate whether Ebola viral factories have a similar effect on immune-related mRNAs in bat kidney cells. I am finalizing my SPARK project with additional experiments and plan to submit my manuscript in two months for peer-review and publication.
What’s next for Jingru?
I am currently at Princeton University for my postdoctoral research training. My research combines molecular virology and quantitative biophysics to establish a link between biophysical principles of viral factories and their biological functions in viral diseases. My goal is to apply this knowledge to uncover how a host’s physiological features (e.g. body temperature) and genetic features shape viral infection, tropism, and evolution in different host species. My long-term goal is to build my own research lab and to train the next generation of scientists who are interested in my research area.