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Archive - Jan 13, 2020

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First-Ever Integration of Metabolism, Expression, Thermodynamics, and ‘Omics Provides Algorithm That Is More Accurate and 10 to 100 Times Faster Than Previous State-of-the-Art Models of Metabolism

All living things are made of carbon, and sugars, e.g. glucose, are a very common source of it. Consequently, most cells are good at eating sugars, using enzymes to digest them through a series of chemical reactions that transform the initial sugar into a variety of cell components, including amino acids, DNA building blocks, and fats. Because they help these sugar-metabolism reactions run efficiently, the enzymes called biocatalysts. Given how critical all enzymes are to life itself, scientists have built several mathematical models that describe how the cells use enzymes to transform a sugar. Such models have been successfully used, for instance, to improve 2nd-generation biofuel production or identify drug targets for malaria, but they don't take into account the metabolic "cost" of producing the enzymes that catalyze all these chemical reactions. Accounting for this phenomenon, called "expression,” is key to describing many other phenomena, including beer fermentation and the growth of cancer cells. But all this first depends on accurately modeling the mechanisms of expression. Now, Professor Vassily Hatzimanikatis at EPFL (Ecole Polytechnique Fédérale de Lausanne)(photo)and Pierre Salvy, a PhD student in his lab, have developed a mathematical model that can efficiently model the expression of enzymes in living cells, as well as its associated metabolic cost. The model is called ETFL for "Expression and Thermodynamics Flux" and draws its accuracy from taking into account both biochemistry and thermodynamics (a set of physico-chemical laws that describe how energy flows in systems). Combining this with mathematical tools from the field of optimization, the researchers were able to drastically improve the accuracy of the model's predictions.

Sestrin Proteins May Provide Benefits of Exercise in Absence of Need to Work Out; Possible Small-Molecule Modulators of Sestrins Might Help Combat Muscle Wasting Due to Age or Disease

Whether it be a brisk walk around the park or high-intensity training at the gym, exercise does a body good. But what if you could harness the benefits of a good workout without ever moving a muscle? Researchers at Michigan Medicine at the University of Michigan and collaborators, studying a class of naturally occurring proteins called Sestrins have found that these proteins can mimic many of exercise's effects in flies and mice. The findings could eventually help scientists combat muscle wasting due to aging and other causes. The results of the researchers’ work were published online on January 13, 2020 in Nature Communications. The open-access article is titled “Sestrins Are Evolutionarily Conserved Mediators of Exercise Benefits.” "Researchers have previously observed that Sestrin accumulates in muscle following exercise," said Myungjin Kim, PhD, a Research Assistant Professor in the Department of Molecular & Integrative Physiology at Michigan Medicine. Working with Professor Jun Hee Lee, PhD, Dr. Kim and a team of collaborating researchers wanted to learn more about the protein's apparent link to exercise. Their first step was to encourage a group of flies to work out. Taking advantage of Drosophila flies' normal instinct to climb up and out of a test tube, collaborators Robert Wessells, PhD, and Alyson Sujkowski, both of Wayne State University in Detroit, developed a type of fly treadmill. Using it, the team trained the flies for three weeks and compared the running and flying abilities of normal flies with those of flies bred to lack the ability to make Sestrin. "Flies can usually run around four to six hours at this point and the normal flies' abilities improved over that period," says Dr. Lee. "The flies without Sestrin did not improve with exercise."