Research Roundup: August 10, 2018

When mitochondria meet metals, a mouse brain atlas, and cancer cell line evolution.

Erik Jacobs
Credit: Erik Jacobs

Welcome to the August 10, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Mitochondria marred by manganese

It’s unclear exactly how heavy metals, such as manganese, are toxic to cells. A team led by Metabolism Program co-director Vamsi Mootha and graduate student Kimberli Kamer found that cellular toxicity from manganese is exacerbated when the metal enters the mitochondria through the organelle’s calcium uniporter. Reporting in PNAS, the researchers discovered that the uniporter’s regulatory subunit MICU1 provides a checkpoint for the channel to discriminate between calcium and manganese, allowing the uniporter to have both high conductance and selectivity. The work opens the door to future studies on the role of mitochondrial manganese in neurodegenerative disorders.

Mouse brain mapped

Connecting the dots from disease-associated gene variant to cell to function remains among the greatest challenges in neuroscience and neuropsychiatric research, a task complicated by the fact that the brain's cellular catalog remains incomplete. In this week's issue of Cell, Arpiar Saunders, associate member Evan Macosko, and institute member Steven McCarroll of the Stanley Center for Psychiatric Research, and colleagues unveiled a cell atlas of the mouse brain, drawn by measuring the gene expression profiles of 690,000 individual cells from nine brain regions. The data, publicly available via a new web portal called DropViz, provide a baseline for studying brain disease-associated genes in mouse-based model systems. Read more in a Broad news story.

Evolution confounds cancer cell line studies

Labs around the world use cancer cell lines for everything from genetic research to drug discovery. The ability to compare results across labs and points in time relies on the assumption that different samples of the same line do not differ in any meaningful way. To test whether this is truly the case, Uri Ben-David, associate member Rameen Beroukhim, core institute member and Cancer Program director Todd Golub, and collaborators ran systematic and comprehensive molecular surveys of several widely used cancer cell lines. Their findings, released in this week's Nature, show that cancer cell lines can evolve in the laboratory in ways that dramatically affect their responses to drugs. The team has launched an online tool, Cell STRAINER, to help scientists benchmark cell line samples from their labs against reference samples. Learn more in a Broad news story and video, and read coverage in STAT+ (paywall), GenomeWeb, and Haaretz.

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In this short video, Uri-Ben David and Todd Golub discuss their efforts to measure how much cancer cell lines evolve in the laboratory, and introduce a new tool, Cell STRAINER, that helps scientists genetically benchmark their cell line samples.