The human DNA molecule, which is more than 2 metres in length, adopts complicated folding patterns to fit inside cells while simultaneously unfolding locally to express genes. The existence of such events, on the other hand, is difficult to measure in experiments, and the theoretical frameworks that explain them continue to be at war with one another.
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Researchers in Italy, Japan, and Poland are attempting to provide a coherent hypothesis for how DNA changes form as genes are expressed. According to the scientists, who published their findings in Biophysics Reviews, a journal published by AIP Publishing, the phenomena of so-called expression waves of gene regulation may be investigated using a statistical mechanics technique.
With this project, the group seeks to bridge a long-standing gap between the two scientific fields that are most interested with the topic.
“A large number of scientists at the nexus of physics and biology are currently attempting to solve what is arguably the most important question in biology,” stated co-author Alessandro Giuliani. “How is it conceivable that, from the same genetic basis in the fertilised egg, around 400 highly differentiated cell types can form, each endowed with a distinct physiological role?” says the researcher.
Transcriptional regulator proteins, also known as transcription factors, are central to many biology-based ideas because they biochemically lead a symphony of genes to be produced in concert. Many physicists, on the other hand, have concentrated their attention on expression waves, which are the rhythmic fluctuations in expression levels across the genome that are caused by the relaxation and condensing of the DNA molecule itself.
“It’s similar to the so-called hola, which is prevalent in soccer and other sporting events, in which the spectators all stand up at the same time, causing a ‘wave’ to spread across the stadium,” Giuliani explained.
In order to get to the heart of the problem, the research is concentrating on a specific type of cell identified in breast cancer that has a demonstrated track record of consistently responding in the same way to many stimuli over time.
In contrast to standard top-down approaches, such as Newton’s laws, they employed statistical mechanics to make sense of how DNA molecules fold by examining the aggregate behaviour of a large number of microscopic actors in terms of ensemble attributes.
The researchers ultimately decided in favour of expression waves, noting that while transcription factors play an important role, they are second fiddle to the changing structure of DNA, which they believe is the most important element.
With the goal of bringing these two perspectives together, the authors present their conclusion using concepts that are common to biology and physics, with mathematics limited to intuitive approaches such as recurrence quantification analysis and the classical statistical method of principal component analysis. They conclude that
Following that, they hope to use the same approach to find ecological tipping points depending on the composition of species in certain environments.
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