Research Roundup: May 11, 2018

The developing zebrafish, tracking malaria genomically, protein capture with CRISPR, and more.

Erik Jacobs
Credit: Erik Jacobs

Welcome to the May 11, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Beneficial bacteria make an immune invitation

In the gut, the immune system does more than fight off harmful microbes — it may actually help beneficial bacteria thrive, which helps the host thrive. To explore how the microbiome is established and maintained, Sarkis Mazmanian at Caltech collaborated with Wen-Chi Chou and Broad institute scientist Ashlee Earl to study the bacterium Bacteroides fragilis. They discovered that B. fragilis alters its cell surface to invite immunoglobulins to bind, which helps anchor the bacterium to the gut epithelium and colonize the gut. Read more in Science and a Caltech press release.

A promising new way to track malaria transmission

Scientists have had success tracking the spread of microbial pathogens by sequencing their genomes, then tracing their lineages through de novo mutations that arise and are passed on in the population. This hadn’t been done in the malaria parasite, Plasmodium falciparum, however; it has a larger genome, it’s relatively slow-evolving, and its mutations tend to occur in repetitive (and thus hard-to-scan) regions of its genome. But a new approach from Broad Institute scientist Daniel Neafsey at the Harvard T.H. Chan School of Public Health, Seth Redmond, and colleagues overcomes these challenges, demonstrating, for the first time, the viability of using de novo mutations to track transmission in a eukaryotic pathogen. Read about it in Molecular Biology and Evolution.

Getting a better handle on gene-regulating proteins

DNA sequencing has revealed a plethora of genomic changes associated with particular cell states. Researchers would love to better understand which proteins drive these changes to get at the underlying mechanistic differences. In Nature Methods, Sam Myers, Broad institute scientist and Proteomics Platform director Steven Carr, and core institute member Feng Zhang, and colleagues unveiled GLoPro (genomic locus proteomics), an approach that uses a "dead" form of Cas9 fused to an engineered form of the enzyme APEX2 to tag proteins adjacent to a desired genomic site with biotin — which researchers can then use to pull proteins out of cells for mass spectrometry analysis. Learn more in a Broad news story.

Zebrafish embryo development, cell by cell

By profiling gene expression in thousands of individual cells during the earliest stages of zebrafish development, a team led by Jeffrey Farrell, Yiqun Wang, Broad core institute member and Klarman Cell Observatory director Aviv Regev, and Broad associate member Alexander Schier at Harvard University has created a comprehensive atlas of embryonic development. The team collected single-cell RNA-sequencing data from 38,731 zebrafish embryo cells and mapped the developmental trajectories of 25 different emerging cell types. Learn the details in Science and a Broad news story. And for more, check out two related papers on vertebrate embryogenesis published by teams at Harvard Medical School. The trio was covered in news stories from HMS, Science, Nature, and Quanta.

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Paper(s) cited

Donaldson GP, et al. Gut microbiota utilize immunoglobulin A for mucosal colonization. Science. Published online May 3, 2018. DOI: 10.1126/science.aaq0926.

Redmond SN, et al. De novo mutations resolve disease transmission pathways in clonal malariaMolecular Biology and Evolution. Published May 1, 2018. DOI: 10.1093/molbev/msy059.

Myers SA, et al. Discovery of proteins associated with a predefined genomic locus via dCas9–APEX-mediated proximity labeling. Nature Methods. Published online May 7, 2018. DOI: 10.1038/s41592-018-0007-1.

Farrell JA, Wang Y, et al. Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis. Science. Published online April 26, 2018. DOI: 10.1126/science.aar3131.