Week in Review: May 18–22

Post-publication peer review via social media; debating the effects of GDF11; human orthologs replace yeast genes; cancer-linked mutations in healthy skin; CRISPR-phage approach to kill antibiotic-resistant bacteria

May 22, 2015
Tracy Vence

Twitter peer review

WIKIMEDIA, RAMALast month, in a series of Twitter posts, Yoav Gilad of the University of Chicago questioned the results of a Mouse ENCODE analysis published in PNAS last year. This week (May 19), Gilad and his coauthor Orna Mizrahi-Man published their reanalysis in an F1000 Research preprint, inviting open, post-publication peer review.

“We shared our analysis in the same way that the original data [were] shared—let the entire community figure it out,” Gilad told The Scientist.

But Michael Snyder of Stanford—one of the authors of the PNAS work who is not convinced that the reanalysis affects his team’s results—did not agree that Twitter was the right forum for such discussion. “Social media is a great forum for other discussions, but not when you’re critiquing someone’s work in this format,” he said.

Steve Phelps of the University of Texas at Austin who was not involved in either study told The Scientist that the recent events reflect well on the state of peer review. “The reanalysis and the participation [from ENCODE researchers] is a pretty positive thing for science,” said Phelps. “The original authors made their data and sources publicly available and shared it readily. [Gilad and Mizrahi-Man] had concerns, and they were able to go into the data and come up with an alternative version.”

“I think that [the discussion] is really pretty healthy and reflects well on both groups,” he added.

Regenerative redux

WIKIMEDIA, DEPARTMENT OF HISTOLOGY, JAGIELLONIAN UNIVERSITY MEDICAL COLLEGEGDF11, a protein that has been shown in mice to decline with age and reverse some aging-related physiologic declines when restored, apparently has the reverse effect: in a study published this week (May 19) in Cell Metabolism, researchers from the Novartis Institutes for Biomedical Research and their colleagues showed that GDF11 did not decline with age in other animals and it inhibited muscle regeneration.

“Both studies are valid. I don’t think one paper is obliterating the other,” said Fabio Demontis, who studies skeletal muscle aging at St. Jude Children’s Research Hospital and was not involved in either study. “The new study indicates that GDF11 is not promoting regeneration in all cases.”

“We believe that . . . there is a very compelling biological explanation for the apparent discrepancies,” Harvard’s Amy Wagers, a coauthor on the work showing levels of the protein declined with age in mice, wrote in an e-mail to The Scientist. “We remain convinced that at least one form of GDF11 declines in blood with age and that maintaining GDF11 levels in an appropriate physiological range is essential for muscle health, as shown by us and now also by Novartis.”

CRISPR-phage attack

WIKIMEDIA, DR GRAHAM BEARDSScientists from Tel Aviv University and their colleagues have used bacteriophages to deliver a specific CRISPR/Cas system into antibiotic-resistant bacteria, sensitizing the microbes to the drugs, they reported this week (May 18) in PNAS.

“It’s a nice application of the CRISPR system to attack resistance genes using phage as a vehicle,” said Michael Terns of the University of Georgia who was not involved in the work.

“The classic phage approach doesn’t distinguish between bacteria that are truly pathogenic versus their very similar neighbors,” said MIT’s Timothy Lu who did not participate in the study. “The idea of CRISPR-based approaches is to enact sequence-specific antimicrobial activity, placing selective pressure against genes that are bad rather than conserved bacterial targets.”

A lot alike

WIKIMEDIA, LILLY_MInserting human homologs to replace faulty genes in yeast can save the microbes from death, researchers from the University of Texas at Austin reported in Science this week (May 21). The results highlight shared function between genes from the two species despite a billion years of evolution separating them.

The results also point to potential applications for medical research, said Madan Babu of the Medical Research Council Laboratory of Molecular Biology in the U.K. who was not involved in the work. “I could put in [yeast] a hundred different variants of the human ortholog and, for example, I could rapidly screen whether they are sensitive to the presence of this or that drug,” he noted.

Mutations in healthy skin

WELLCOME TRUST SANGER INSTITUTE, INIGO MATINCORENACancer-free skin that has been exposed to the sun harbors a variety of potential disease-causing mutations near cancer-associated genes, researchers from the Wellcome Trust Sanger Institute in the U.K. and their colleagues showed in Science this week (May 21).

“It’s a nice exposé of the spatial distribution of mutations in clinically normal skin, quantifying the number of mutations present and showing, for the first time in a comprehensive way, that cancer genes are mutated in normal skin that has been chronically sun exposed,” said Kenneth Tsai of the MD Anderson Cancer Center in Houston, Texas, who was not involved in the work.

Other news in life science:

Clinical Epidemiology Pioneer Dies
Evidence-based medicine advocate David Sackett has passed away at age 80.

Yeast–Made Opioid Progresses
Scientists are one step closer to coaxing engineered yeast to produce morphine from a simple sugar.

Artificial Trachea Researcher Found Guilty of Misconduct
An independent investigator says that the surgeon misrepresented the truth in papers about artificial trachea transplants.

CRISPR “Kill Switches” for GMOs
Researchers create an inducible method to remove specific genes and even kill escaped genetically modified organisms.