Living organisms find a critical balance

Interdisciplinary ASU study finds cell networks seek optimal point between stability and adaptiveness


October 4, 2018

Biologists know a lot about how life works, but they are still figuring out the big questions of why life exists, why it takes various shapes and sizes and how life is able to amazingly adapt to fill every nook and cranny on Earth.

An interdisciplinary team of researchers at Arizona State University has discovered that the answers to these questions may lie in the ability of life to find a middle ground, balancing between robustness and adaptability. The results of their study were recently published in Physical Review Letters. Scientists Sara Walker, Bradley Karas, Siyu Zhou, Bryan Daniels, Harrison Smith, Hyunju Kim with 67 sheets of paper, one for each of the biological networks studied in this research. Download Full Image

The importance of stability

The research team, led by Bryan Daniels of the Center for Biosocial Complex Systems with direction from faculty member Sara Walker of the School of Earth and Space Exploration, sifted through data to better understand the root connections among 67 biological networks that describe how components of these systems interact with one another. The biological networks are sets of individual components (like proteins and genes) that interact with one another to perform important tasks like transmitting signals or deciding a cell's fate. They measured a number of mathematical features, simulating the networks’ behavior and looking for patterns to provide clues on what made them so special.

To perform their study, they examined data from the Cell Collective database. This rich resource represents biological processes across life — encapsulating a wide range of biological processes: from humans, animals, plants, bacteria and viruses. The number of components in these networks ranged from five nodes to 321 nodes, encompassing 6,500 different biological interactions.

And these nodes include many of life’s key building blocks — genes and proteins that act as master switches controlling cell division, communication, growth and death.

Using a wealth of molecular data, scientists can now study the interactions among the building blocks, with an ultimate goal of understanding the key to how life emerges.

“We wanted to know whether the biological networks were special compared to random networks, and if so, how,” Daniels said.

They focused on trying to find a threshold point at which an entire system may change in response to just a small change. Such a change could profoundly upset the balance of life, creating a teeter-totter of fate deciding whether an organism would die or thrive.

“In a stable system, organisms will always come back to their original state,” Daniels explained. “In an unstable system, the effect of a small change will grow and cause the whole system to behave differently.”

Through rigorous testing of the 67 networks, the team found that all of the networks shared a special property: They existed in between two extremes, neither too stable nor unstable.

As such, the team found that sensitivity, which is a measure of stability, was near a special point that biologists call “criticality,” suggesting that the networks may be evolutionarily adapted to an optimal tradeoff between stability and instability.

Life in the balance

Previous studies have shown that a handful of biological systems, from neurons to ant colonies, lie in this middle ground of criticality and this new research expands the list of living systems in this state.

This can be of particular interest to astrobiologists like co-author Walker, who is searching for life on other planets. Understanding how life can take various forms, and why it does so, may help identify life on other planets and determine how it might look different from life on Earth. It can also help inform our search for the origins of life in the lab.    

“We still don’t really understand what life is,” Walker said. “Determining what quantitative properties, such as criticality, best distinguish life from nonlife is an important step toward building that understanding at a fundamental level so that we may recognize life on other worlds or in our experiments on Earth, even if it looks very different than us.”  

The findings also advance the field of quantitative biology by showing that, from the basic building blocks of life, scientists can identify a critical sensitivity that is common across a large swath of biology. And it promises to advance synthetic biology by allowing scientists to use life’s building blocks to more accurately construct biochemical networks that are similar to living systems.

“Each biological system has distinctive features, from its components and its size to its function and its interactions with the surrounding environment,” said co-author Hyunju Kim of the School of Earth and Space Exploration and the Beyond Center. “In this research, for the first time, we are able to make connections between the theoretical hypothesis on biological systems’ universal tendency to retain the balance at the medium degree of stability and 67 biological models with various characteristics built on actual experiment data.”

In addition to Daniels, Walker and Kim, the interdisciplinary research team on this study includes co-authors Douglas Moore of the Beyond Center, Siyu Zhou of the Department of Physics, Bradley Karas and Harrison Smith of the School of Earth and Space Exploration, and Stuart Kauffman of the Institute for Systems Biology in Seattle.

This research emerged from a course led by Walker and Kim on complex systems approaches to understanding life, offered at the School of Earth and Space Exploration. Co-authors Karas, Zhou and Smith were originally students in the class when the project began. 

“In our class project, the analytic tools and codes to study general dynamical systems were provided, and we gave the option for students to choose any dynamical systems they were interested in,” Kim said. “Students were asked to modify the analysis and codes to study various features of each selected system. As a result, we ended up dealing with many different biological networks, investigating more diverse aspects of those systems, and developed more codes and analysis tools, even after the completion of the class.”

Joe Caspermeyer contributed to this article.

Karin Valentine

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Thunderbird prof says Brexit may not be as bad as expected


October 4, 2018

It’s less than six months until the U.K. is scheduled to leave the European Union. As the March 29, 2019, deadline for Brexit approaches, there are still several key goals and parliamentary hurdles to overcome. 

Britain is facing the country’s biggest shift in foreign and trade policy in more than 40 years. Businesses, economists and government officials on both sides of the English Channel talk about uncertainty as the deadline approaches. Thunderbird Prof Robert Grosse Says Brexit May Not Be as Bad As Expected Download Full Image

Prime Minister Theresa May is challenging her political opponents to back her plan for Brexit — or risk “panic” and “chaos." But not everyone believes that Brexit will cause such chaos for the U.K. and those countries that do business with it. 

One such expert is Robert Grosse, professor of business administration and director for Latin America at Thunderbird. He expects that Brexit will have little impact on either the European Union or the United States.

Whether Brexit turns out to be a Y2K moment — much ado about nothing — or total chaos, as deadlines near it is undeniably causing uncertainty around trade, migration and regulation. Read more in the Thunderbird Knowledge Network overview: Brexit update: What you need to know.

ASU Now asked Grosse to elaborate:

Question: You’ve said that Brexit will not have the impact that some people fear. Can you explain? 

Answer: I expect that Brexit will have very little effect on the U.S. or on the EU. Business will go on as usual, with probably a zero tariff agreement initially between the EU and U.K. until a few specific restrictions might be imposed. The choice to leave the EU had nothing to do with tariffs and everything to do with immigration and the EU budget. Still, trade will probably be marginally affected, because there will need to be documentation of products shipped between the U.K. and the EU. This can be done electronically, so it might not make much difference at all.

The impact will be small in Europe, other than the question of the border between the two Irelands. The U.K. could find some financial service activity moving to Frankfurt, Germany, or elsewhere as a retaliation by the EU and because the EU countries are jealous of London’s position as the world’s financial capital. I do not expect that much will actually change.

Robert Gross, Ph.D., Thunderbird Professor of International Business & Director, Latin America
Robert Grosse

Q: Are you optimistic that the U.K. and EU will come up with a solid exit agreement in time for the March 2019 deadline? Or do you think an extension will be negotiated?

A: I feel pretty sure that an exit agreement will not be reached by the deadline. Politicians prefer to reach agreements under panic situations, so they can blame the outcome on that factor, rather than taking an economic view of what arrangement would be best. Brexit is a populist political statement, not really an economic one — except for the British objecting to a too-large contribution to the EU budget. They might come to some agreement in March 2019, but I definitely doubt that they will do so until the deadline has been reached. 

The optimal economic solution for all concerned is for the U.K. to remain in the EU, and even this outcome is possible under pressure at the end — but I expect that the U.K. will leave, just as they stayed out of the Common Market for 15 years after the main European countries started it in 1958.

Q: What do you see as the stumbling blocks to a smooth withdrawal agreement, if any? 

A: The U.K. government cannot go against the majority vote that was in favor of Brexit, despite many or even most of the legislators and government leaders seeing Brexit as a bad idea. So, they won’t work toward a "smooth" agreement, since many of them don’t want to proceed anyway.

Q: It seems that much of the concerns about Brexit's impact center on timing — concerns that businesses will have to deal with significantly altered trade processes without enough time to get ready. Do you think these fears are overstated? 

A: Yes, they certainly are overstated.

Q: Do you have any tips for U.S. or European companies that do business with the U.K., Scotland or Ireland as the split approaches?  

A: Diversify your business into the EU, to avoid hassles on transportation of products and movement of your employees that may occur for months after Brexit is finalized. Don’t lose sleep over it, however, since the impacts will be quite limited.

Q: CEOs of several U.K.-based companies have announced stockpiling supplies or moving resources, including people, to Europe. Is that unnecessary?

A: It is a very valuable step to take to demonstrate to the public that the companies are taking risk seriously. I do not think it is necessary in an economic sense, but because perceptions are hugely important in business, the companies should take visible steps to protect themselves — but they should not spend too much money doing so.

Q: Do you think Britain will leave the EU by March 2019?  

A: Probably by default, because they won’t have taken any concrete steps to undo Brexit, at least until that time. 

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