Brendan M. Lynch
KU News Service

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.”

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Wanna Skype? Chancellor gets creative to surprise Truman winner. See it here:
Rock Chalk! Junior Ashlie Koehn named KU's 18th Truman Scholar
Ashlie Koehn, a University of Kansas junior from Burns studying in Kyrgyzstan, interrupted helping her host family prepare dinner to make a Skype call on Monday evening.

.@KU bschool 's KIP team includes @KU _SADP students in all-ages housing project. #KUworks
Wanna Skype? Chancellor gets creative to surprise Truman winner From KU News Service: Ashlie Koehn, a University of Kansas junior from Burns studying in Kyrgyzstan, interrupted helping her host family prepare dinner to make a Skype call on Monday evening. To her surprise, Chancellor Bernadette Gray-Little was on the other end of the call letting Koehn know she had been named a 2015 Harry S. Truman Scholar. Koehn is the 18th KU student to be named a Truman Scholar and the only 2015 recipient from the state of Kansas. Earlier this month, she was also named a 2015 Udall Scholar. And in spite of a distance of more than 10,800 kilometers and 11 time zones, Koehn’s thrill from hearing the news from the chancellor came through loud and clear. “Ashlie’s experience at KU epitomizes a quality undergraduate experience. She challenged herself in her coursework, exposed herself to different research opportunities, studied abroad in Germany, Switzerland and Kyrgyzstan, and participated in both student government and community service projects,” Gray-Little said. “This is quite a year for Ashlie. Her hard work is a wonderful reflection on her and also a great reflection on the university, and we all congratulate her.” Each new Truman Scholar receives up to $30,000 for graduate study. Scholars also receive priority admission and supplemental financial aid at some premier graduate institutions, leadership training, career and graduate school counseling, and special internship opportunities within the federal government. Koehn, a member of KU’s nationally recognized University Honors Program, is majoring in environmental studies, economics and international studies. Her goal after earning her KU degree is to pursue a master’s degree in economics at either the London School of Economics or the University of Reading, with a focus on the economics of climate change. In 2014, she received KU’s Newman Civic Engagement Award for her work establishing the Coalition against Slavery and Trafficking. Her involvement with the issue was sparked by Hannah Britton, associate professor of political science and women, gender, and sexuality studies, who hosted national conference on contemporary slavery at KU three years ago. “Ashlie and I met several times to think about what KU students could contribute to the issue of slavery and human trafficking, and the result was her founding of KU CAST,” Britton said. “After a year as president, Ashlie successfully handed the organization over to the next student leader. She demonstrated her strong leadership qualities by setting a unique goal and then pursuing it with her sense of passion, engagement and dedication. No matter the country or context, her leadership strength is evident in her coursework, her public service and her work experiences.” The University Honors Program works with a campus committee to select KU’s nominees for the Truman Scholarship and supports them during the application process. Anne Wallen, assistant director of national fellowships and scholarships, noted it was an amazing ruse to pull off the surprise. Originally, the call was set up to be between Wallen and Koehn. “I was totally not prepared to be greeted by Chancellor Gray-Little, but it was an amazing surprise for sure,” Koehn said. “As a first-generation student, it took time to learn the collegiate system, but my parents taught me to be resourceful and independent from a young age and KU and the Kansas Air National Guard have provided me with the opportunities to drive me into the future, both at graduate school and in my career. I plan to use the Truman Scholarship to pursue a career as an environmental economist helping to shape future trade agreements and leverage action on important international environmental issues, particularly concerning climate change.” Koehn also had a surprise of her own for the chancellor — the meal she was helping to prepare was not exactly typical Kansas dinner fare. On the menu with her host family in Kyrgyzstan on Monday was a traditional Kyrgyz meal called Beshbarmak, or “five fingers,” because you eat it with your hands. The dish is made of horse and sheep and was being prepared as a birthday celebration for Koehn’s host mom. Chancellor Gray-Little, as she signed off from Skype, made sure to encourage Koehn to enjoy her Beshbarmak. Koehn is the daughter of Rodney and Carolyn Koehn of Burns. She graduated from Fredric Remington High School in Moundridge. She is an active member of the Kansas Air National Guard and currently on leave while studying abroad in Bishkek, Kyrgyzstan. She is a member of the KU Global Scholars Program and a past member of the Student Senate. In addition to being named a 2015 Truman and Udall scholar, she was named a 2014 Boren Scholar and Gilman Scholar and in 2013 was named the Kansas Air National Guard Airman of the Year.

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