Mapping the motion of molecules: NIH awards ASU biophysics professor more than $2.5M

By

Dominique Perkins

Arizona State University Professor Steve Pressé was recently awarded more than $2.5 million from the National Institutes of Health as principal investigator for two independent awards. 

Pressé is an associate professor in both the Department of Physics and the School of Molecular Sciences and a member of the Center for Biological Physics initiative, which seeks to apply a computational physics approach to understanding biological phenomena. 

These grants will support two independent projects developing methods to extract information on processes occurring deep within living cells. The ability to directly monitor the movement of biomolecules, their assembly into larger clusters, as well as their disassembly within cells, would shed immediate insight into the rules of life.

Adding a little light

There are millions of biomolecules within living cells and trillions of cells within a complex living organism. However, despite how small or insignificant they may seem, it is individual biomolecules, moving and interacting within the cells that contain them, that play the role of primary actors dictating how life unfolds. The catch? They are difficult, not to say impossible, to see in their native environment. 

What’s more, gleaning useful information from the complicated data gathered when monitoring them is far from obvious. Sometimes the fundamental logic of missile tracking technology is the most help in tracking biomolecules. 

Yet missiles and biomolecules present very different scientific problems. 

To begin with, unlike missiles, molecules themselves cannot be directly imaged. Each of the millions of molecules in a cell is nearly identical to another, and special care is needed to track the movement of even just a few. By attaching a light-emitting molecule and examining the ratio of signals to background noise in each pixel of the camera, the positions can be deduced. However, when the biomolecules cross paths, the physics of light as it is emitted makes it difficult to distinguish one from the other. 

The goal of Pressé’s first project is to develop the mathematics needed to deduce the paths of many molecules even as they interact and crisscross the cellular environment. 

A smaller focus 

While the first NIH grant is concentrated on gathering detailed information to deduce entire tracks of biomolecules, it relies on gathering a lot of light — the data from the light-emitting molecules attached to the biomolecular tracks. Gathering a lot of light takes time. 

However, biomolecular events can occasionally happen very quickly. Therefore, new tools are needed to see these. 

Pressé’s second project aims to find new ways to observe and capture data on these processes. If we could learn information from just one light particle, just one pixel on a camera, very quickly, this would tremendously improve the time resolution of data imaging. However, it would also make the new data more difficult to interpret. 

Making sense of it all 

A common thread — and a common challenge — in both projects is data processing and the limited ability of our current mathematics to make sense of the complex data at the molecular scale. Interpreting the data is a delicate process, and at times, even more crucial to the success of the projects than the observation methods themselves. 

Fortunately, the computational capabilities of today’s technology have greatly improved. 

“We can now store large quantities of data today, analyze them and get answers to what biomolecules are doing inside cells if we have the right analysis tools,” Pressé said. “This, in turn, will allow us to not only be descriptive about life’s processes but quantitative as well.” 

More to come

If we had a microscope that could peer into biological samples and reveal each minute happening in exquisite detail — the replication of DNA and how that information is transmitted and processed by the rest of the cell — we would have such a clear understanding of life. No disease would remain a mystery.  

Unfortunately, cells make it very difficult to view and address these answers. Instead, we rely on a combination of imperfect measurements and rudimentary, but improving mathematics, to begin to unravel life’s mysteries.

New methods of observation and computational data analysis from research like Pressé’s will open the doors to more revelations moving forward, and improve our understanding of life and the world around us, one step at a time.