Chaotic swings in the concentration of a particular protein — what in mathematics is known as chaotic dynamics — can increase the activation of a number of genes that are otherwise not activated, University of Copenhagen researchers have found. Based upon a range of experimental results, the researchers arrived at their conclusions through mathematical calculations and theoretical arguments.

The researchers investigated how the protein NF-kB, produced within cells, stimulates genes. Among other things, this particular protein is vital for maintaining the body’s immune defense system and thereby the body’s ability to combat disease.

The concentration of NF-kB fluctuates over time, and these swings affect the genes and therefore the condition of cells. In other words, when in a chaotic state, the NF-kB protein is most effective at activating genes and optimally “tuning” the immune system.

“The results can have a tremendous impact on our understanding of how the immune system functions and how the incidence of some of the most serious illnesses, including diabetes, cancer, and Alzheimer’s, might be avoided. For example, we know that cancer is related to a failure of signaling within the body. So, to avoid cancer, it is imperative to have the right dynamic at work in cells,”

says Mogens Høgh Jensen, a professor in biocomplexity at the University of Copenhagen’s Niels Bohr Institute.

Differential Gene Regulation

The researchers believe that this new knowledge can be part of future therapies.

“These could come in the form of new medications that ensure proper protein function. Therapies could also involve the withdrawal and testing of cells from a body to gauge whether cells are in the right condition to have the correct swings. If they aren’t, it may be possible to predict and discover illnesses before they occur,”

explains Mathias Heltberg, a PhD student in biocomplexity.

[caption id=“attachment_98248” align=“aligncenter” width=“900”]Dynamics from coupled oscillators and emergence of chaos Dynamics from coupled oscillators and emergence of chaos
Credit: . Heltberg, et al CC-BY[/caption]

The research results are among the first to prove that chaos can be an important aspect of the mechanisms that steer the enormous complexity characteristic of all living things. The discovery even surprised the researchers, as chaotic dynamics are often seen as something that living organisms seek to avoid.

The new knowledge opens up an entirely new understanding of how gene regulation is possible through varied swings in the proteins that control them.

“Chaos is a mathematically well-defined dynamic, one that, for example, has previously been used to explain great changes in weather systems. With the enormous complexity that characterizes higher order living things, it is evident that chaotic dynamics will occur in different types of systems. But how chaos plays a decisive role in living cells is entirely new,”

concludes Høgh Jensen.

Mathias L. Heltberg, Sandeep Krishna & Mogens H. Jensen On chaotic dynamics in transcription factors and the associated effects in differential gene regulation Nature Communications volume 10, Article number: 71(2019)

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