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Lehigh researchers to study Ebola method of host cell invasion


Anand Jagota (left) and Xiaohui (Frank) Zhang.

Viruses cause diseases ranging from the common cold to the deadly and highly infectious Ebola disease. Their methodology is to enter healthy cells -- often like the proverbial Trojan Horse -- by hijacking normal physiological processes, tricking the cell to let them inside.

For this reason, a principal difficulty in designing therapies against viruses lies in the fact that attempts to stop them from entering a cell are also likely to affect normal physiological processes.

The Ebola virus, for example, infects healthy cells by disguising itself as debris (wastes or remains) from dead cells. Healthy cells, whose normal function is to clear up this debris, mistakenly take up Ebola and become infected.

But there is hope. Differences always exist between a virus and debris particles. If studied carefully, it may be possible to design therapies that can block specific virus entry while leaving normal physiological cellular processes intact.

Two researchers from Lehigh University were awarded an NSF grant to explore the possibilities.

Anand Jagota, founding chair of the bioengineering department and professor of bioengineering and the chemical and biomolecular engineering departments, is the principal investigator for a study entitled "TIM Protein-Mediated Ebola Virus-Host Cell Adhesion: Experiments and Models." The grant's co-principal investigator, Xiaohui (Frank) Zhang, is an assistant professor in bioengineering and the mechanical engineering and mechanics department.

"For us to be successful in our exploration," Jagota said, "it is necessary to understand virus uptake processes in quantitative detail, both experimentally and theoretically -- and particularly the latter, which is the main goal of this project."

Their work will build upon on separate studies that use atomic-force microscope-based technologies to measure the binding forces between molecules.

"Our focus is to develop understanding of the behavior of collections of adhesion molecules, which are proteins on cell surfaces that cause cells to bind to other cells or particles," Zhang added. "Ultimately, our goal is to develop a predictive model for how an entire virus particle adheres to a cell prior to its uptake."

This project is complementary to a related research program funded by the NIH. A critical component of the research in the NSF-funded program is modeling the deformation of virus and cell particles in order to quantitatively measure their properties. If successful, the projects will contribute to establishing an experimentally validated, quantitative connection between biology-based models for virus entry into cells and the properties of the virus and the cell.

Additionally, the interdisciplinary nature of the research will provide excellent educational and research opportunities for graduate and undergraduate students. The research team will also design a new exhibit for a local, hands-on science museum based upon their work.

Da Vinci Science Center in Allentown, Pennsylvania is an independent, non-profit organization that promotes hands-on science learning through inquiry, highlights vibrant and important career opportunities in science available to every young person and encourages all people to be curious and creative.

The planned exhibit will demonstrate the physical and mechanical details of virus uptake and how such study could lead to new therapies for a virus infection -- or perhaps even a cure.

- Mary Anne Lynch '16G

July 16, 2018

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