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Math Discovery provides new method to study cell activity, aging, MSU research shows

5/20/24
By: Meg Henderson

Galen Collins, assistant professor in MSU's 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.

We already understand how quickly proteins are made, which can happen in a matter of minutes, said Collins, who is also a scientist in the Mississippi Agricultural and Forestry Experiment Station. "Until now, we've had a very poor understanding of how much time it takes them to break down."

The paper in applied mathematics, "Maximum entropy determination of mammalian proteome dynamics," presents the new tools that quantify the degradation rates of cell proteins how quickly they break down helping us understand how cells grow and die and how we age. Proteins complex molecules made from various combinations of amino acids carry the bulk of the workload within a cell, providing its structure, responding to messages from outside the cell and removing waste.

"For certain kinds of scientific questions, experiments can often reveal infinitely many possible answers; however, they are not all equally plausible," said lead author Alexander Dear, research fellow in applied mathematics at Harvard University. "The principle of maximum entropy is a mathematical law that shows us how to precisely calculate the plausibility of each answer it's entropy so that we can choose the one that is the most likely."

"This 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," Collins said. "Maximum entropy gives us a clear and precise picture of how protein degradation occurs in cells."

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.

They also explored how a shift in the breakdown of certain cell proteins contributes to neurodegenerative disease.

"These diseases occur when waste proteins, which usually break down quickly, live longer than they should," Collins said. "The brain becomes like a teenager's bedroom, accumulating trash, and when you don't clean it up, it becomes uninhabitable."

Dear affirmed the study''s 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.

"Our work provides a powerful new experimental method for quantifying protein metabolism in cells, he said. "Its simplicity and rapidity make it particularly well suited for studying metabolic changes."

Collins's 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's 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.

It's an incredible honor to be published in PNAS, but it was also a lot of fun being part of this team," Collins said. "And it's very meaningful to see my former mentor's body of work wrapped up and published."

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 www.pnas.org. The Mississippi Agricultural and Forestry Experiment Station conducts research that improves human health and well being. Learn more at www.mafes.msstate.edu.

Mississippi State University is taking care of what matters. Learn more at www.msstate.edu.

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