This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Imagine a brain teaser where the challenge is to spot the difference between two nearly identical sandcastles. The removal of three grains of sand.
Scientists face a similarly exasperating challenge when looking at changes in protein levels within our cells, where small fluctuations can mean the difference between health and disease or a drug working and not working. A new study in Cell, led by Steven Banik, assistant professor of chemistry in the School of Humanities and Sciences and institute scholar at Sarafan ChEM-H, provides a solution to this problem, offering a new tool to amplify and visualize these tiny changes. "Our ideas about what's important in biology are often defined by the tools that we have to look at it," said Banik.
"There's a lot of biology happening inside a black box that we can't see. If we can amplify signals that we haven't been able to see before, we can discover new biology or new molecules that might have therapeutic benefit." Proteins are the molecular machines inside cells that perform all the duties necessary for life. Layers of regulatory machinery govern how much of a certain protein is produced in a cell at any given time, and different kinds of cells contain distinct repertoires of proteins that coordinate what they do—a cardiac cell contains the protein machinery to produce a heartbeat, while a brain cell is equipped with proteins that allow it to fire.
Small decreases in the levels of these proteins can have major consequences for cellular behavior. Being able to study these small changes is also important when developing medicines; using a drug to degrade a rogue, malfunctioning protein can help treat diseases like cancer. However, few techniques are sensitive enough to detect these changes in proteins that are not very abundant to begin with, and it can be difficult to study more than one protein or drug molecule at a time.
Traditional techniques for measuring protein abundance often rely on extracting proteins from many cells and then concentrating the one you want to study to visualize it. This is like panning for gold on a beach until you find enough gold flecks to make a pile that you can see without a magnifying glass. You probably would need a dump truck of sand to get enough gold.
To accelerate drug discovery by more quickly zeroing in on the most promising drug candidates, Banik and his team sought to devise a more sensitive method that would allow them to pan for gold with small volumes of sand, or in this case, small numbers of cells in a high-throughput screen. "If you have many grains of sand dispersed all over a table, and you take one grain away, it would be very hard to see that," explained Banik. "But if we had a way to make the grain of sand look like a boulder and then took it off the table, that would be noticeable.
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