Menagerie of Chromosome Contact Patterns
Science & Technology

Biologists Construct a “Periodic Table” for Cell Nuclei – And Discover Something Strange, Baffling and Unexpected

In a paper printed in Science, biologists at Baylor School of Medication, the Netherlands Most cancers Institute and Rice College learning the tree of life unveil a new classification system for cell nuclei and the invention of a methodology for transmuting one sort of cell nucleus into one other. This illustration reveals the menagerie of chromosome contact patterns within the nuclei of varied animals and crops. Credit score: Graphic by Adam Fotos, Olga Dudchenko, Benjamin Rowland and Erez Lieberman Aiden/Baylor School of Medication

100 fifty years in the past, Dmitri Mendeleev created the periodic desk, a system for classifying atoms based mostly on the properties of their nuclei. This week, a group of biologists learning the tree of life has unveiled a new classification system for cell nuclei, and found a methodology for transmuting one sort of cell nucleus into one other.

The research, which seems this week within the journal Science, emerged from a number of once-separate efforts. One centered on the DNA Zoo, a global consortium spanning dozens of establishments together with Baylor School of Medication, the Nationwide Science Basis-supported Heart for Theoretical Organic Physics (CTBP) at Rice College, the College of Western Australia and SeaWorld.

Scientists on the DNA Zoo group had been working collectively to categorise how chromosomes — which will be a number of meters lengthy — fold as much as match contained in the nuclei of various species from throughout the tree of life.

“Whether or not we have been taking a look at worms or urchins, sea squirts or coral, we saved seeing the identical folding patterns arising,” stated Olga Dudchenko, co-first writer of the brand new research and a member of The Heart for Genome Structure at Baylor and CTBP.

Biologists at Baylor School of Medication, the Netherlands Most cancers Institute and Rice College present in a research printed in Science that the nuclear association in a human cell will be changed into that typical of a fly. Credit score: Illustration by Evgeny Gromov

Ultimately, the group realized it was simply seeing variants on two total nuclear designs. “In some species, chromosomes are organized just like the pages of a printed newspaper, with the outer margins on one facet and the folded center on the different,” defined Dudchenko, who can also be co-director of DNA Zoo. “And then in different species, every chromosome is crumpled into a little ball.”

“So we had a puzzle,” stated Erez Lieberman Aiden, an affiliate professor and Emeritus McNair Scholar at Baylor, co-director of the DNA Zoo and senior writer on the brand new research. “The information implied that over the course of evolution, species can swap again and forth from one sort to the opposite. We puzzled: What’s the controlling mechanism? May or not it’s attainable to vary one sort of nucleus into one other within the lab?” Aiden can also be director of The Heart for Genome Structure and a senior investigator at CTBP.

An artist’s interpretation of chromatin folded up contained in the nucleus. A research of the terribly lengthy contour of folded DNA led by biologists at Baylor School of Medication, the Netherlands Most cancers Institute and Rice College revealed nature’s methodology for transmuting one sort of cell nucleus into one other. Credit score: Mary Ellen Scherl

In the meantime, an unbiased group within the Netherlands had found one thing surprising. “I used to be doing experiments on a protein referred to as condensin II, which we knew performs a position in how cells divide,” stated Claire Hoencamp, co-first writer of the research and a member of the laboratory of Benjamin Rowland on the Netherlands Most cancers Institute. “However we noticed the strangest factor: After we mutated the protein in human cells, the chromosomes would completely rearrange. It was baffling!”

The 2 groups met at a convention within the Austrian mountains, the place Rowland offered his lab’s newest work. They quickly realized that Hoencamp had hit on a solution to convert human cells from one nuclear sort to a different.

An artist’s interpretation of evolution from primates, through trendy people to mosquitoes. This paintings is a play on information gathered by biologists at Baylor School of Medication, the Netherlands Most cancers Institute and Rice College that reveals the group of the human genome can become one thing that resembles the genome group of mosquitoes. Credit score: Joris Koster/Netherlands Most cancers Institute

“After we appeared on the genomes being studied on the DNA Zoo, we found that evolution had already finished our experiment many, many occasions! When mutations in a species break condensin II, they often flip the entire structure of the nucleus,” stated Rowland, senior writer on the research. “It’s all the time a little disappointing to get scooped on an experiment, however evolution had a very lengthy head begin.”

The group determined to work collectively to verify condensin II’s position. However then the COVID-19 pandemic struck, and a lot of the world shut down.

“With out entry to our laboratories, we have been left with just one solution to set up what condensin II was doing,” Hoencamp stated. “We would have liked to create a laptop program that might simulate the consequences of condensin II on the chain of tons of of thousands and thousands of genetic letters that comprise every human chromosome.”

A picture reveals an origami-like sequence of the human chromosome 14-folded into a three-dimensional sample. Biologists at Baylor School of Medication research how the genomes of various organisms throughout the tree of life fold in 3D. Credit score: Jason Ku, Erik Demaine/Baylor School of Medication

The group turned to José Onuchic, the Harry C. and Olga Ok. Wiess Chair of Physics at Rice. “Our simulations confirmed that by destroying condensin II, you possibly can make a human nucleus reorganize to resemble a fly nucleus,” stated Onuchic, co-director of CTBP, which incorporates collaborators at Rice, Baylor, Northeastern College and different establishments in Houston and Boston.

The simulations have been carried out by a group inside Onuchic’s lab at CTBP led by postdoctoral fellow and co-first writer Sumitabha Brahmachari, working with Vinicius Contessoto, a former postdoc at CTBP, and Michele Di Pierro, a CTBP senior investigator and at present an assistant professor at Northeastern College.

“We started with an extremely broad survey of two billion years of nuclear evolution,” Brahmachari stated. “And we discovered that a lot boils down to 1 easy mechanism, that we will simulate in addition to recapitulate, on our personal, in a take a look at tube. It’s an thrilling step on the highway to a new type of genome engineering — in 3D!”

Reference: “3D genomics throughout the tree of life reveals condensin II as a determinant of structure sort” by Claire Hoencamp, Olga Dudchenko, Ahmed M. O. Elbatsh, Sumitabha Brahmachari, Jonne A. Raaijmakers, Tom van Schaik, Ángela Sedeño Cacciatore, Vinícius G. Contessoto, Roy G. H. P. van Heesbeen, Bram van den Broek, Aditya N. Mhaskar,#, Hans Teunissen, Brian Glenn St Hilaire, David Weisz, Arina D. Omer, Melanie Pham, Zane Colaric, Zhenzhen Yang, Suhas S. P. Rao, Namita Mitra, Christopher Lui, Weijie Yao, Ruqayya Khan, Leonid L. Moroz, Andrea Kohn, Judy St. Leger, Alexandria Mena, Karen Holcroft, Maria Cristina Gambetta, Fabian Lim, Emma Farley, Nils Stein, Alexander Haddad, Daniel Chauss, Ayse Sena Mutlu, Meng C. Wang, Neil D. Younger, Evin Hildebrandt, Hans H. Cheng, Christopher J. Knight, Theresa L. U. Burnham, Kevin A. Hovel, Andrew J. Beel, Pierre-Jean Mattei, Roger D. Kornberg, Wesley C. Warren, Gregory Cary, José Luis Gómez-Skarmeta, Veronica Hinman, Kerstin Lindblad-Toh, Federica Di Palma, Kazuhiro Maeshima, Asha S. Multani, Sen Pathak, Liesl Nel-Themaat, Richard R. Behringer, Parwinder Kaur, René H. Medema, Bas van Steensel, Elzo de Wit, José N. Onuchic, Michele Di Pierro, Erez Lieberman Aiden and Benjamin D. Rowland, 28 Could 2021, Science.
DOI: 10.1126/science.abe2218

Work at Rice, Baylor and Northeastern was supported by the Nationwide Science Basis (NSF), the Welch Institute, the Nationwide Institutes of Well being, the NSF-supported Behavioral Plasticity Analysis Institute, IBM, the Pawsey Supercomputing Heart and Illumina Inc.

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