A Lawrence Livermore National Laboratory physicist¹ and his colleagues have found a new application for the tools and mathematics typically used in physics to help solve problems in biology. Specifically, the team used statistical² mechanics and mathematical modeling to shed light on something known as epigenetic（后生的） memory -- how an organism can create a biological memory of some variable condition, such as quality of nutrition or temperature.

 

"The work highlights the interdisciplinary（各学科间的） nature of modern molecular⁴ biology, in particular, how the tools and models from mathematics and physics can help clarify problems in biology," said Ken⁵ Kim, a LLNL physicist and one of the authors of a paper appearing in the Feb. 7 issue of Physical Review Letters.

 

Not all characteristics of living organisms can be explained by their genes⁶ alone. Epigenetic processes react with great sensitivity to genes' immediate⁷ biochemical surroundings -- and further, they pass those reactions on to the next generation.

 

The team's work on the dynamics⁸ of histone protein modification⁹ is central to epigenetics. Like genetic³ changes, epigenetic changes are preserved when a cell divides. Histone proteins were once thought to be static, structural¹⁰ components¹¹ in chromosomes¹², but recent studies have shown that histones（组蛋白） play an important dynamical role in the machinery¹³ responsible for epigenetic regulation.

 

When histones undergo chemical alterations¹⁴ (histone modification) as a result of some external stimulus¹⁵, they trigger short-term biological memory of that stimulus within a cell, which can be passed down to its daughter cells. This memory also can be reversed after a few cell division cycles.

 

Epigenetic modifications¹⁶ are essential in the development and function of cells, but also play a key role in cancer, according to Jianhua Xing, a former LLNL postdoc and current professor at Virginia Tech. "For example, changes in the epigenome can lead to the activation¹⁷ or deactivation¹⁸ of signaling pathways that can lead to tumor¹⁹ formation," Xing added.

 

The molecular mechanism²⁰ underlying²¹ epigenetic memory involves complex interactions between histones, DNA²² and enzymes²³, which produce modification patterns that are recognized by the cell. To gain insight into such complex systems, the team constructed a mathematical model that captures the essential features of the histone-induced epigenetic memory. The model highlights the "engineering" challenge a cell must constantly face during molecular recognition. It is analogous²⁴ to（与……类似） restoring a picture with missing parts. The molecular properties of a species have been evolutionarily selected to allow them to "reason" what the missing parts are based on incomplete information pattern inherited from the mother cell.

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