Contact: Meg Henderson
STARKVILLE, Miss.鈥擭ew mathematical tools revealing how quickly cell proteins break down are poised to uncover deeper insights into how we age, according to a recently published paper co-authored by a Mississippi State researcher and his colleagues from Harvard Medical School and the University of Cambridge.
Galen Collins, assistant professor in MSU鈥檚 Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, co-authored the groundbreaking paper published in the Proceedings of the National Academy of Sciences, or PNAS, in April.
鈥淲e already understand how quickly proteins are made, which can happen in a matter of minutes,鈥 said Collins, who is also a scientist in the Mississippi Agricultural and Forestry Experiment Station. 鈥淯ntil now, we鈥檝e had a very poor understanding of how much time it takes them to break down.鈥
The paper in applied mathematics, 鈥,鈥 presents the new tools that quantify the degradation rates of cell proteins鈥攈ow quickly they break down鈥攈elping us understand how cells grow and die and how we age. Proteins鈥攃omplex molecules made from various combinations of amino acids鈥攃arry the bulk of the workload within a cell, providing its structure, responding to messages from outside the cell and removing waste.聽
The results proved that not all proteins degrade at the same pace but instead fall into one of three categories, breaking down over the course of minutes, hours or days. While previous research has examined cell protein breakdown, this study was the first to quantify mathematically the degradation rates of all cell protein molecules, using a technique called maximum entropy.
鈥淔or certain kinds of scientific questions, experiments can often reveal infinitely many possible answers; however, they are not all equally plausible,鈥 said lead author Alexander Dear, research fellow in applied mathematics at Harvard University. 鈥淭he principle of maximum entropy is a mathematical law that shows us how to precisely calculate the plausibility of each answer鈥攊ts 鈥榚ntropy鈥欌攕o that we can choose the one that is the most likely.鈥
鈥淭his kind of math is sort of like a camera that zooms in on your license plate from far away and figures out what the numbers should be,鈥 Collins said. 鈥淢aximum entropy gives us a clear and precise picture of how protein degradation occurs in cells.鈥
In addition, the team used these tools to study some specific implications of protein degradation for humans and animals. For one, they examined how those rates change as muscles develop and adapt to starvation.
鈥淲e found that starvation had the greatest impact on the intermediate group of proteins in muscular cells, which have a half-life of a few hours, causing the breakdown to shift and accelerate,鈥 Collins said. 鈥淭his discovery could have implications for cancer patients who experience cachexia, or muscle wasting due to the disease and its treatments.鈥
They also explored how a shift in the breakdown of certain cell proteins contributes to neurodegenerative disease.
鈥淭hese diseases occur when waste proteins, which usually break down quickly, live longer than they should,鈥 Collins said. 鈥淭he brain becomes like a teenager鈥檚 bedroom, accumulating trash, and when you don鈥檛 clean it up, it becomes uninhabitable.鈥
Dear affirmed the study鈥檚 value lies not only in what it revealed about cell protein degeneration, but also in giving scientists a new method to investigate cell activity with precision.
鈥淥ur work provides a powerful new experimental method for quantifying protein metabolism in cells,鈥 he said. 鈥淚ts simplicity and rapidity make it particularly well-suited for studying metabolic changes.鈥
Collins鈥檚 post-doctoral advisor at Harvard and a co-author of the article, the late Alfred Goldberg, was a pioneer in studying the life and death of proteins. Collins noted this study was built on nearly five decades of Goldberg鈥檚 research and his late-career collaboration with mathematicians from the University of Cambridge. After coming to MSU a year ago, Collins continued collaborating with his colleagues to complete the paper.
鈥淚t鈥檚 an incredible honor to be published in PNAS, but it was also a lot of fun being part of this team,鈥 Collins said. 鈥淎nd it鈥檚 very meaningful to see my former mentor鈥檚 body of work wrapped up and published.鈥
Since 1914, PNAS has been one of the most authoritative publications of high-impact research in the biological, physical and social sciences. More information and past issues can be found at . The Mississippi Agricultural and Forestry Experiment Station conducts research that improves human health and well-being. Learn more at . 聽
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