How your immune system uses chaos to prevent disease

Modern research has unearthed many of the faulty mechanisms that are at play in cancer, yet science has plenty left to discover.

On a cellular level, some of these mechanisms revolve around what medical experts call signaling pathways. Cell signaling pathways regulate the growth, survival, and proliferation of cells.

In cancer, some signaling proteins are hyperactive, leading to the growth and proliferation of tumor cells, while others — which would normally act as tumor suppressors — are not functioning correctly.

Understanding the dynamic that is at play within cells is, therefore, key to preventing and overcoming cancer and many other chronic diseases.

New research may have broken new ground in this respect, as three scientists have discovered a new mechanism of cell regulation: chaos.

Doctoral researcher Mathias Heltberg and professor Mogens Høgh Jensen — both from the Niels Bohr Institute at the University of Copenhagen in Denmark, together with Sandeep Krishna from the National Centre for Biological Sciences in Bangalore, India, set out to investigate how a particular protein stimulates gene activity.

The scientists found that chaotic dynamics is the answer. The protein they studied is Nuclear factor-κB (NF-kB).

NF-kB is key to keeping the body’s immune system alert and functional. So the findings may help stave off more than cancer: diabetes and Alzheimer’s disease could also be targets if researchers understand better how the body’s natural defenses work.

Chaos is essential for immune response

NF-kB is a transcription factor that is critical for both “innate and adaptive immune functions,” and it also mediates inflammatory responses. As a result, its levels in the body fluctuate with time, affecting gene and cell function.

Recent studies have shown that NF-kB signaling also plays a crucial role in cancer, providing the link between cancer development and inflammation.

In the current study, Prof. Jensen and his colleagues used mathematical calculations and lab experiments to show that chaotic ups and downs in NF-kB concentrations activate genes that would otherwise stay silent.

The NF-kB protein needs to be in a chaotic state in order to activate the right genes that allow for the optimal immune response, the study showed.

Until now, researchers believed that all living organisms avoided chaotic dynamics. But the new study challenges this belief, as the researchers show that chaotic swings in protein concentrations are critical for activating key genes.

“Chaos is a mathematically well-defined dynamic, one that, for example, has previously been used to explain great changes in weather systems,” explains Prof. Jensen.

“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,” the researcher adds.

Implications for diabetes, cancer, Alzheimer’s

The researchers also note the therapeutic implications of the findings. New medications, says Heltberg, the study’s co-author, could “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,” continues Heltberg.

“If they aren’t, it may be possible to predict and discover illnesses before they occur.”

Prof. Jensen concurs:

“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.”

Prof. Mogens Høgh Jensen

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