Research Roundup: April 26, 2019

New insights into Friedreich’s ataxia, William’s syndrome, and the human gut microbiome.

Kelly Davidson
Credit: Kelly Davidson

Welcome to the April 26, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

A breath of “fresh air” for ataxia cells

Friedreich's ataxia (FRDA) is a progressive, neurodegenerative movement disorder caused by mutations in the gene for the mitochondrial protein frataxin, which helps in the synthesis of essential iron-sulfur clusters. A team led by postdoctoral scholars Tslil Ast, Joshua Meisel, and institute member and Metabolism Program co-director Vamsi Mootha found that yeast, human cells, and nematodes lacking the frataxin protein can survive if grown in extremely low oxygen levels. Featured in Cell and a Broad news story, the work showed that hypoxia restores iron-sulfur clusters and normalizes FRDA-associated signaling events. In a mouse model of FRDA, breathing low oxygen slowed progression of ataxia, while higher oxygen levels did the reverse.

Watching new bugs set up house in your gut

From a bacterium's point of view, the environment in each person's intestines is a little different, but how bacteria evolve to fit everyone's unique gut has been a mystery. By profiling mutations in one common gut microbe, Bacteroides fragilis, a team led by graduate student Shijie Zhao, affiliate member Tami Lieberman and institute member Eric Alm of the Infectious Disease and Microbiome Program found at least sixteen genes that evolved repeatedly within the same individuals. These genes are largely involved in cell membrane construction and fiber digestion, suggesting that their rapid evolution helps B. fragilis adapt to new hosts. Learn more in Cell Host & Microbe and a Cell Press press release.

Mice study provides molecular insights into hypersociability

Williams syndrome (WS), a neurodevelopmental disorder characterized by intellectual disability and hypersociability, is caused by spontaneous deletion of 26 genes on chromosome 7. Of those 26, general transcription factor IIi (Gtf2i) is linked to hypersociability in WS, although the underlying mechanisms are poorly understood. A team led by institute member Guoping Feng in the Stanley Center for Psychiatric Research and colleagues selectively deleted Gtf2i in the excitatory neurons of the mouse forebrain and characterized changes in the brain. The team found that Gtf2i knockout mice show WS-relevant abnormalities and they were able to reverse the symptoms of the disease in mice ― thus providing molecular clues for exploring potential therapeutic targets. Read more in Nature Neuroscience and MIT News.

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