The biological network in cells helps the body adapt to stresses on health – ScienceDaily

Every minute of every day, our body is adjusting to the needs of each moment. When we overeat on carbs, exercise, or get sick, chemical reactions within our cells work, slow down, or change strategy so we get the energy and strength we need.

All of this happens without our knowledge, and perhaps explains why so little is understood about how the body feels and responds to these constant demands. In search of answers to this question, scientists at the University of Utah Health have led research that opens up a whole new world inside our cells. Their study was published in Sciencesreveals a vast network of interactions that indicate how cells adapt in real time to withstand stresses on our health.

“We’re discovering how nature evolved to ‘medicate’ proteins and their pathways,” says Jared Rutter, PhD, distinguished professor in the Department of Biochemistry at the University of Utah and corresponding author of the study. “By following nature’s lead, we are learning how to make better treatments.”

These findings—and the technology that made them possible—became the basis for the biotechnology company Atavistik Bio, which Rutter co-founded. The company is leveraging this new understanding to accelerate drug discovery for metabolic diseases and cancer.

On a more fundamental level, Rutter says, the advances deepen knowledge about how cells and our bodies work.

New frontiers

The network described in the study represents an underappreciated layer of regulation in cells that comes from an unexpected source. For nearly 20 years, Rutter’s lab has researched metabolism, the chemical reactions that produce energy and build up essential ingredients to keep cells running smoothly. Their new research finds that the intermediate products of those chemical reactions are more than passive building blocks and fuel sources for cells, as has long been thought.

Instead, these intermediate products, together with other metabolites, form an extensive network of sentinels that monitor the environment and prompt cells to adapt when needed. They do this by interacting with proteins and modifying the way they work. Does a large meal pump too many carbs into the body? Or a lot of fat? Like a railroad switch directing a train onto a new track, these protein-metabolite interactions shift metabolic processes to break down those nutrients and stabilize the track.

Dr. Kevin Hicks, first author of the study, developed a new technology called MIDAS, which reveals the magnitude of the regulatory network that acts as an interface between environmental signals and cell metabolism, called protein-metabolite interaction. The highly sensitive technology has identified interactions that have not been seen before. An analysis of 33 human proteins involved in converting carbohydrates into fuel found 830 interacting with metabolites. Given that there are thousands of proteins in a cell, the full extent of the network is expected to be much larger.

“It’s surprising how little we know the extent of these interactions,” says Hicks. “We are pushing our understanding of the biological network in new directions.”

Metabolic processes that go awry can lead to illness and disease. Highlighting additional interactions in the network, Rutter and Hicks say, will lead to a better understanding of the root causes of diseases — and the development of new therapeutic approaches to get things back on track.

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