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Time lapse of a developing drosophila embryo. (Credit: Carlos Sanchez-Higueras/Hombría lab/CABD)

Every animal, from an ant to a human, contains in their genome pieces of DNA called Hox genes. Architects of the body, these genes are keepers of the body’s blueprints; they dictate how embryos grow into adults, including where a developing animal puts its head, legs and other body parts. Scientists have long searched for ways to decipher how Hox genes create this body map; a key to decoding how we build our bodies.

Now an international group of researchers from Columbia University and the Spanish National Research Council (CSIC) based at the Universidad Pablo de Olavide in Seville, Spain have found one such key: a method that can systematically identify the role each Hox gene plays in a developing fruit fly. Their results, reported recently in Nature Communications , offer a new path forward for researchers hoping to make sense of a process that is equal parts chaotic and precise, and that is critical to understanding not only growth and development but also aging and disease.

“The genome, which contains thousands of genes and millions of letters of DNA, is the most complicated code ever written,” said study co-senior author Richard Mann , PhD, principal investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute and a faculty member in the Department of Systems Biology . “Deciphering this code has proven so difficult because evolution wrote it in fits and starts over hundreds of millions of years. Today’s study offers a key to cracking that code, bringing us closer than ever to understanding how Hox genes build a healthy body, or how this process gets disrupted in disease.”

Read the full article at the Zuckerman Institute

Tal Korem, PhD
Dr. Tal Korem

Tal Korem, PhD, has been named a CIFAR Azrieli Global Scholar, a fellowship that supports leading early-career researchers in science and technology. 

Dr. Korem is an assistant professor of systems biology with a joint appointment in obstetrics and gynecology at Columbia University Vagelos College of Physicians & Surgeons, and a faculty member of the Program for Mathematical Genomics . As a global scholar, he is joining CIFAR’s Humans and the Microbiome research program, where his work will focus on harnessing human microbial communities to identify and develop novel diagnostic and therapeutic tools.

CIFAR’s  Azrieli Global Scholars program supports its fellows through funding and mentorship, emphasizing essential network and professional skills development. The scholars join CIFAR research programs for a two-year period where they collaborate with fellows and brainstorm new approaches to pressing science and technology problems. Research topics are diverse, ranging from bio-solar energy and visual consciousness to engineered proteins and the immune system. 

Dr. Korem is one of 14 researchers out of an applicant pool of 217 selected by the Canadian-based nonprofit organization. This year’s cohort represents citizenship in eight countries and appointments in institutions from Canada, the U.S.,  Israel, Australia, the Netherlands, and Spain.

-Melanie A. Farmer

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)

Biologists 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 Bioinformatics. 

Protein engineering is a relatively young field that creates new proteins never seen before in nature. Today’s protein engineers usually create synthetic proteins by making small changes to the gene that encodes a naturally occurring protein. The variety of synthetic proteins range from stain-removing enzymes that have improved detergents to a long-acting insulin that’s used by millions of people with diabetes.

But two big unsolved challenges for protein engineers remain: The gene encoding the synthetic protein needs to be contained to prevent escape into other organisms and the gene needs to resist mutating over time so the protein doesn’t lose its function.

By merging two genes into a single DNA sequence, Columbia University synthetic biologists have created a method that could prevent human-engineered proteins from spreading into the wild, as well as stabilize synthetic proteins so they don’t change over time. The work, recently published in Science, was developed by Harris Wang, PhD, assistant professor of systems biology, with graduate student, Tomasz Blazejewski and postdoctoral scientist, Hsing-I Ho, PhD. 

In devising the method, the researchers were inspired by overlapping genes in viruses. When two different genes overlap, they occupy the same sequence of DNA. But the genes are read in different frames so that two different proteins are produced.

In overlapping genes, a random mutation in the sequence may not affect one gene, but it’s likely that it will harm the second gene.

“Overlapping genes essentially lock in a specific DNA sequence, and we thought we could exploit this idea for synthetic biology ...Ten years ago, we didn’t have the technology that would make this possible,” says Dr. Wang. “We didn’t have enough sequences in the database to make informed predictions and we didn’t have a way to synthesize long DNA sequences for testing our predictions.”

The gut microbiome–composed of hundreds of different species of bacteria–is a complex community and a challenge for scientists to unravel. One specific challenge is the spatial distribution of different microbes, which are not evenly distributed throughout the gut. A new method developed by the lab of Dr. Harris Wang should help scientists locate and characterize these neighborhoods, which could shed light on how microbes influence the health of their hosts.

Techniques that can identify all species in the gut microbiome only work with homogenized samples (like stool), but methods that preserve spatial information can only cope with a handful of species.

Dr. Wang, assistant professor of systems biology and of pathology & cell biology, and graduate student Ravi Sheth in the Department of Systems Biology, tested the new technique with mice who switched from a low-fat to a high-fat diet. Diet is known to change the abundance of specific bacteria in the gut within days, but the new technique also revealed that the switch caused wholesale changes of microbial neighborhoods.

“Specific regions of bacteria were entirely lost with a switch in diet,” Sheth says. “This was exciting to us as it will give us clues to understanding how that change happens and how the change may impact health.”

Read the full article in the CUIMC Newsroom

The research, titled “Spatial metagenomic characterization of microbial biogeography in the gut,” was published July 22 in Nature Biotechnology.