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Research reveals evolution of cells’ signaling networks in diverse organisms

Wed, 04/16/2014

LAWRENCE — Cells use protein-signaling networks to process information from their surroundings and respond to constantly changing environments. This includes information about the presence or absence of vital nutrients as well as the presence of other cells. Signaling networks control the decisions that cells make in response to these conditions.  

In a paper just published in the influential Proceedings of the National Academy of Sciences, researchers from the University of Kansas shed light on protein-signaling networks used by bacterial cells and why they are so different from the more complex networks found in eukaryotes, such as human beings.

“Our research focuses on elucidating the general principles that underlie how signaling networks work in a variety of organisms,” said Eric Deeds, assistant professor at KU’s Center for Bioinformatics and Department of Molecular Biosciences. “We’re helping people understand why they observe the types of networks that they do in different cells.”

According to Deeds, a better understanding of information processing inside human cells will lead to more rational approaches to targeting complex diseases like cancer.

“In bacterial systems, our work could help lead to the development of novel antibiotic strategies as well as the engineering of new information processing capabilities in bacterial cells,” he said.

Human cells possess very complex networks with many interconnected pathways. Bacteria, on the other hand, utilize very simple networks in which most pathways are completely isolated from one another.

“It’s like the contrast between a telephone wire and a complicated computer chip,” said Deeds. “A telephone wire connects one person to another directly and simply transmits the signals from one end to the other. This is like the bacterial signaling pathways, which have a simple topology directly connecting inputs to outputs. In contrast, a computer chip is highly interconnected, with many downstream elements responding to any given input. This kind of integrated architecture allows a computer to perform complex signal-processing tasks. The architecture of human signaling networks is similar to that of a computer chip, with a much more complicated topology and a much richer possible set of input-output relationships.”

The paper in PNAS authored by Deeds and KU graduate research assistant Michael Rowland shows that this global difference in network structure ultimately derives from the properties of the atomic “building blocks” from which the networks themselves are constructed. 

“In particular, the enzymes used in bacterial-signaling networks are often bifunctional, in that they catalyze both the modification and de-modification of their protein substrates,” Deeds said.

The research showed that these bifunctional enzymes become progressively less efficient as they work on larger numbers of substrates. This prevents them from evolving the extensive levels of “crosstalk” that characterize eukaryotic networks. In contrast, the enzymes employed by human cells are “monofunctional,” leading to “remarkably different” global architectures.

“Monofunctional enzymes basically represent a ‘division of labor,’” Deeds said. “There is one protein that performs the phosphorylation step — called the kinase — and another that performs the dephosphorylation step, called the phosphatase. Our work has shown that dividing things up like this allows human networks to achieve high levels of crosstalk, producing the complex integrated architectures that perform decision-making tasks for our cells. Bacterial networks, which use a single enzyme to perform both those tasks, simply can’t exhibit high levels of crosstalk.”

Moving ahead, Deeds’ work aims to achieve a firmer understanding of the crosstalk that characterizes complex protein signaling in humans.

“Although it’s clear that human networks can and do have massive amounts of crosstalk, we currently don’t understand exactly what these systems are doing,” said Deeds. “Fully answering that question is a major area of research both for my lab and for a large number of other labs around the world.”



When looking to tackle the issue of obesity in rural America, where should we start? The answer is not what you might think. Empathy, says Christie Befort, an associate professor at KU who has just won a $10 million award from the Patient-Centered Outcomes Research Institute to investigate solutions to rural obesity. Many physicians are embarrassed talking about weight—especially in a small town where everybody knows each other, Befort says. By providing obesity treatment options in rural primary care, she plans to start a conversation, and maybe a revolution, in rural health care. For more details on Befort's efforts, check out the 2015 Chancellor's Report: http://bit.ly/1D5A5MO and her video: http://bit.ly/1C5xYZa Tags: #KUcommunities #Obesity #Health #Rural #Midwest Patient-Centered Outcomes Research Institute - PCORI

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Explore KU: Experience a KU Men's Basketball tradition It’s explosive. It’s dramatic. It’s intimidating. It’s a KU tradition (see more at http://bit.ly/KUtraditions) simply known as the Confetti Toss. But it creates a primal eruption of fan enthusiasm at the opening of every KU men’s basketball game at Allen Fieldhouse. It starts as the visiting team is introduced on court. The KU student section is visibly bored and unimpressed. The entire section under the north basket holds up University Daily Kansans — making the point they’d rather read the newspaper than even look at the other team. They shake and rustle the student newspapers. Then the moment they were waiting for arrives — the Jayhawks enter the court. All Rock Chalk breaks loose. Newspapers, confetti and thousands of thundering voices soar into already charged atmosphere of KU’s hallowed basketball arena. The confetti hits its high point, near the banner on the north wall reading “Pay Heed, All Who Enter: Beware of the Phog.” And the confetti rains back into the stands, onto the court and into the memories of all at hand. It’s time to play.


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