Biophysical Tools Key to Understanding How Ebola Spreads

On most days, biophysicists go about their work with little public interest.  The things they work on are complex, very specific, and impossible to see with the naked eye. Every once in a while though, biophysicists find their work in the spotlight due to public events such as a disease outbreak. With the ebola outbreak in west Africa in the news, the research of Biophysical Society members Michelle Digman, University of California Irvine, and Robert Stahelin, University of Notre Dame has attracted increased attention. Digman was kind enough to answer some questions about her work for us.

Actin cytoskeleton (red) and Ebola VP40 virus budding (green).

Actin cytoskeleton (red) and Ebola VP40 virus budding (green).

What is the connection between your research and Ebola?

My research aims are to develop enabling technologies in optical microscopy to be able to measure protein dynamics in living cells. These fluorescent fluctuation measurements measure spatial-temporal interaction at the molecular scale in real time. My colleague, Professor Robert Stahelin at the Indiana University School of Medicine and the University of Notre Dame, who is studying protein-lipid interactions in the life cycle of the Ebola virus, wanted us to use these biophysical approaches to measure the membrane binding behavior of the Ebola virus matrix protein, VP40. Given that we both are interested in understanding protein regulation and function we teamed up to understand how VP40 from the Ebola virus assembles into virus like particles (VLPs) in live cells.

Why is your research important to those concerned about finding a cure/stopping the spread of Ebola?

Our research involves studying the egress of the virus particles and understanding the mechanism of spreading. There is not a large body of literature that addresses how the ebola virus assembles and how it interacts with endogenous proteins, lipid membranes, or cytoskeletal structures in living cells. I think this information can be useful in developing small molecule targets for therapy.

How did you get into this area of research?

This collaboration, with Stahelin, started mutual interests to learn more about virus protein interactions in living cells. Our microscopic tools allowed us to measure protein assembly, aggregation and interactions. We realized once the VP40 protein was expressed in live cells with a fluorescent tag that the best way to follow protein assembly was to use dual color particle tracking.

How long have you been working on it?

We have been collaborating for 3 years.

Do you receive federal funding for this work? 

Yes, I am the Co-PI of the Laboratory for Fluorescence Dynamics (LFD) which is a P41 Biomedical Technology Resource Center (BTRC) funded by NIGMS at NIH. We have 5 core technological research projects, over 10 driving biological problems, collaborative research projects as well as training and dissemination of the technologies developed at the LFD. As such, our work with Stahelin also included training one of his graduate students, Emmanuel Adu Gyamfi, who spearheaded this project for his Ph.D. thesis.

Have you had any surprise findings thus far? 

Everything we learned with the Ebola VP40 protein was a surprise. It was never studied before in living cells and in real time. Using the number and molecular brightness (N&B) and with the 3D particle tracking methods, we were able to calculate the aggregation process on the actin filaments.

What is particularly interesting about your work on the Ebola VP40 protein from the perspective of other researchers?

The Ebola VP40 protein is sufficient to make virus like particles from human cells.  Thus, we study the assembly of one single virus particle at a time directly inside the cell to understand the spatial and temporal distribution of VP40 within the plasma membrane before a new virus particle leaves the cell membrane.

What is particularly interesting about your research from the perspective of the public?

With the recently identified structural information on VP40 that came available from Dr. Saphire’s lab at The Scripps Research Institute, we are starting to unravel the mechanism of how new virus particles are formed to sustain and spread Ebola infections.

With Ebola a top story in the news, are you receiving more inquiries about your work?  Does the attention to the disease affect you in other ways?

Yes, mostly from family and friends. Stahelin, on the other hand, has appeared on a local news broadcast, been interviewed on a radio show, and interviewed by the local newspaper.   has received the most inquiries.

 

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