Media contact: Julie Kiefer, Julie.kiefer@hsc.utah.edu
Every minute of every day, our body adapts to meet the needs of each moment. When we binge on carbs, exercise, or become sick, chemical reactions inside our cells switch on, slow down, or shift strategy so that we have the energy and strength we need.
All this happens without us knowing it, perhaps explaining why so little is understood about how the body senses and responds to these constant demands. Seeking answers to this question, scientists at led research that opens up a whole new world within our cells. Their study, published in , uncovers a vast network of interactions that suggest how cells adjust in real time to withstand stresses on our health.
鈥淲别鈥檙别 discovering how nature has evolved to 鈥榙rug鈥 its own proteins and pathways,鈥 says , distinguished professor in the Department of Biochemistry at University of Utah and the study鈥檚 corresponding author. 鈥淏y following nature鈥檚 lead, we鈥檙e learning how to make better therapeutics.鈥
These findings鈥攁nd the technology that made them possible鈥攈as become the basis for the biotechnology company , co-founded by Rutter. The company is leveraging this new understanding to accelerate drug discovery for metabolic diseases and cancer.
At a more fundamental level, Rutter says, the advance deepens knowledge about how cells and our bodies work.
A New Frontier
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鈥檚 lab has researched metabolism, the chemical reactions that produce energy and build essential components to keep cells running smoothly. Their new research finds that intermediate products of those chemical reactions are more than passive building blocks and sources of fuel for cells, as had long been thought.
Instead, these intermediate products, along with other metabolites, make up an expansive web of sentries that monitor the environment and prompt cells to adapt when needed. They do this by interacting with proteins and modifying how they work. Does a big meal pump too many carbs in the body? Or too much fat? Like a railroad switch that guides a train onto a new track, these protein-metabolite interactions shift metabolic operations to break down those nutrients and steady the course.
The study鈥檚 first author Kevin Hicks, Ph.D., developed a new technology, termed MIDAS, that reveals the enormity of the regulatory network that acts as an interface between environmental cues and cell metabolism, called the protein-metabolite interactome. The highly sensitive technique identified interactions that had never been seen. An analysis of 33 human proteins involved in converting carbohydrates into fuel found 830 interactions with metabolites. Given that there are thousands of proteins in the cell, the full scale of the network is predicted to be much larger.
鈥淚t鈥檚 surprising how little we know about the extent of these interactions,鈥 Hicks says. 鈥淲e are pushing our understanding of the biological
network in new directions.鈥
Metabolic processes that become derailed can lead to illness and disease. Rutter and Hicks say that shedding light on additional interactions in the network will lead to a better understanding of root causes of diseases鈥攁nd the development of new therapeutic approaches for getting things back on track.
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The research published as 鈥溾 and was a multi-institutional collaboration with support from multiple organizations including the National Institutes of 星空传媒, Calico Laboratories the Nora Eccles Treadwell Foundation, and the Howard Hughes Medical Institute. See the publication for full listings.