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Biologists Develop 'Periodic Table' For Cell Nuclei

The new table, by an international team, could lead to a new method of genome engineering.

A cross-organizational team of biologists developed a new classification system for cell nuclei, and consequently uncovered a method for transmuting one type of cell nucleus into another, a press statement from Rice University explains.

The periodic table was created over 150 years ago by Dmitri Mendeleev as a system for classifying elements based on the ascending number of electrons in an atom. The team of biologists behind the new "periodic table" for cell nuclei used Mendeleev's original table, as well as their knowledge of the tree of life, as inspiration for their own project.

The team, who published their findings in the journal Science, believe the new table and discovery could lead to an all-new method of genome engineering.

Chromosome-based classification systems

The work on the nuclei cell table started with scientists from a consortium called the DNA Zoo studying classification systems for chromosomes based on the ways in which they fold up to fit inside the nuclei of different species of animals.

"Whether we were looking at worms or urchins, sea squirts or coral, we kept seeing the same folding patterns coming up," said Olga Dudchenko, co-first author of the new study and a member of The Center for Genome Architecture at Baylor and CTBP.

Biologists Develop 'Periodic Table' For Cell Nuclei
An illustration showing chromosome contact patterns in the nuclei of several animals and plants. Source: Adam Fotos, Olga Dudchenko, Benjamin Rowland and Erez Lieberman Aiden/Baylor College of Medicine

The team eventually realized it was simply seeing variants on two overall nuclear designs: "in some species, chromosomes are organized like the pages of a printed newspaper, with the outer margins on one side and the folded middle at the other,” explained Dudchenko. "And then in other species, each chromosome is crumpled into a little ball."

These findings implied that, over millennia of evolution, species are able to switch back from one type to another.

Working with the protein condensing II

In a bid to uncover the mechanism behind their discovery, and to ascertain whether it might be possible to change one type of nucleus into another in a lab, the team from DNA Zoo teamed up with a group of scientists from the laboratory of Benjamin Rowland at the Netherlands Cancer Institute (NCI).

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The NCI team had been working on experiments with a protein called condensing II, which plays a role in cell division.

When they mutated this protein in human cells, the team from NCI made a surprising observation:

"When we mutated the protein in human cells, the chromosomes would totally rearrange," Claire Hoencamp, co-first author of the study and a member of the NCI team explained. "It was baffling!"

Converting human cells from one nuclear type to another

The two teams started to collaborate after they came to the realization that Hoencamp's discovery essentially provided a method for converting human cells from one nuclear type to another.

"When we looked at the genomes being studied at the DNA Zoo, we discovered that evolution had already done our experiment many, many times! When mutations in a species break condensin II, they usually flip the whole architecture of the nucleus," said Benjamin Rowland, senior author of the study. "It’s always a little disappointing to get scooped on an experiment, but evolution had a very long head start."

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Confined to their homes due to the pandemic, the teams turned to artificial intelligence to verify their findings. They developed simulation models that showed that, by destroying condensin II, a human nucleus could be reorganized to resemble a nucleus of another species, such as a fly. 

"We began with an incredibly broad survey of two billion years of nuclear evolution," said co-first author Sumitabha Brahmachari. "And we found that so much boils down to one simple mechanism, that we can simulate as well as recapitulate, on our own, in a test tube."

The researchers say their work forms a part of a new era in gene editing — recent breakthroughs such as the new gene-editing tool CRISPRoff herald an age of "genetic engineering 2.0." As Brahmachari put it, the team's work is "an exciting step on the road to a new kind of genome engineering — in 3D!"

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