Detailed Map Gives Scientists a New Window into how Human-Infecting Viruses Work

Sagi Shaipra PHIPSTer Cell Paper
Researchers implement P-HIPSTer, an in silico computational framework that leverages protein structure information to identify approximately 282,000 protein-protein interactions across all fully-sequenced human-infecting viruses (1001 in all). This image highlights that in addition to rediscovering known biology, P-HIPSTer has yielded a series of new findings and enables discovery of a previously unappreciated universe of cellular circuits and biological principles that act on human-infecting viruses. (Image Courtesy of Dr. Sagi Shapira)

Researchers at Columbia University Irving Medical Center have leveraged a computational method to map protein-protein interactions between all known human-infecting viruses and the cells they infect. The method, along with the data that it generated, has spawned a wealth of information toward improving our understanding of how viruses manipulate the cells that they infect and cause disease. Among its findings, the work uncovered a role for estrogen receptor in regulating Zika Virus (ZIKV) infection, as well as links between cancer and the human papillomavirus (HPV).

The research, led by Sagi Shapira , PhD, Assistant Professor in the Department of Systems Biology and the Department of Microbiology & Immunology at Columbia University Vagelos College of Physicians and Surgeons , appears today in the journal, Cell . Dr. Shapira’s collaborators include Professors Barry Honig , PhD, of Systems Biology and of Biochemistry and Molecular Biophysics and Raul Rabadan , PhD, of Systems Biology and of Biomedical Informatics.

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June 03, 2019

These Creatures Are Helping Us Understand Our Genome

Oxytricha

New research by Laura Landweber, PhD, who has joint appointments in the Department of Biochemistry and Molecular Biophysics, the Department of Systems Biology and the Department of Biological Sciences at Columbia University, is being featured by Columbia Univeristy Iriving Medical Center Newsroom.

As reported, a new study of a single-celled eukaryote with 16,000 tiny chromosomes may shed light on a recently discovered feature of the human genome.

Methyladenine, or 6mA—a modification of DNA common in Oxytricha trifallax—has only recently been found in multicellular organisms, with some studies suggesting a role in human disease and development.

Finding the enzymes that lay down the methyl marks will be critical to understanding what 6mA is doing in Oxytricha and other organisms, but the enzymes have been difficult to identify.

The new research—to be published in the June 13 issue of Cell—reveals how 6mA marks are made to the Oxytricha genome and suggests why the enzymes have been hard to find.

Read more about the Oxytricha genome and the Landweber lab’s new insights into 6mA and its potential role in human diseases.

Dr. Landweber has been studying Oxytricha for two decades and previously uncovered its 16,000 chromosomes. (See related Faculty Q+A and video.)

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October 10, 2018

Q+A with Dr. Laura Landweber

Oxytricha. (Credit: Bob Hammersmith)

Laura Landweber, PhD, loves a challenge. So it’s no surprise that she has built a scientific career unraveling the hows and whys of a unique single-cell organism known for its biological complexity.

An evolutionary biologist whose work sits at the interface of genetics and molecular biology, Dr. Landweber, for nearly 20 years, has focused much of her research on Oxytricha trifallax , a microbial organism that is prevalent in ponds, feeds on algae and has a highly complex genome architecture, making it an attractive, albeit challenging, model organism to study. Compared to humans, with 46 chromosomes containing some 25,000 genes, Oxytricha is known to comprise many thousands of chromosomes, in the ballpark of 16,000 tiny “nanochromosomes”. Yet not only is it complex in sheer numbers of chromosomes but the information carried in those individual chromosomes can be scrambled, like information compression, and the process of development in Oxytricha must descramble this information so that it can be converted into RNA and proteins.

“DNA can be flipped and inverted in Oxytricha and the cellular machinery actually knows how to restore order,” says Dr. Landweber. “Hence, it’s this wonderful paragon for understanding genome integrity and the maintenance and establishment of genome integrity.”

Even more perplexing, in cell division, Oxytricha reproduces asexually when it wants to produce more in number, and it reproduces sexually when it needs to rebuild its genome. It also has the ability to “clean up” its genome, so to speak, eliminating nearly all of the non-coding DNA, or so-called junk DNA. Much of why Oxytricha presents such an intricate genomic landscape remains a mystery, and for Dr. Landweber, the leading expert on this single-celled protist, that wide-open field for potential discovery is what got her hooked.

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