Research Roundup: February 15, 2019

Detailing NeuroGAP's plans, probing side chains' purpose, and examining a channel gate's structure.

Erik Jacobs
Credit: Erik Jacobs

Welcome to the February 15, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Getting to know NeuroGAP-Psychosis

The psychosis project of the Stanley Center for Psychiatric Research's NeuroGAP initiative aims to  ethically and collaboratively expand our knowledge of the genetics of psychiatric disease in African populations and build capacity in Africa for psychiatric genetics research. In BMJ Open, Anne Stevenson, associate member Karestan Koenen, and colleagues describe the study's impetus, aims, and research plan, with particular emphasis on ethical patient recruitment and research capacity building. The team also celebrated enrollment of their 5,000th participant this week.

Selecting for side chains

In the world of biopolymer libraries, Philip Lichtor, core institute member and Merkin Institute for Transformative Technologies in Healthcare director David Liu, and colleagues reported that collections with access to nonpolar side chains outperform libraries without these additions. The researchers created sequence-defined polymer libraries with a variety of charged, polar, and nonpolar side chains, and selected for the ability to bind proteins PCSK9 and IL-6. The libraries with access to nonpolar side chains generally outcompeted other libraries, with more rapid sequence convergence and higher binding affinities. The work also suggests how proteins, which have nonpolar side chains, might have an evolutionary advantage for some tasks compared to nucleic acid polymers that lack these groups. Learn more in Nature Chemical Biology.

Channeling insights about a calcium channel

Mitochondrial calcium uniporter, a transmembrane protein that allows the transport of calcium ions into a cell’s mitochondria, is regulated by two proteins called MICU1 and MICU2. Although it is known that MICU1 and MICU2 work together to inhibit the calcium transport channel, researchers did not completely understand how each of these proteins contributes to this channel's regulation. Reporting in PNAS, Kimberli Kamer, institute member and Metabolism Program co-director Vamsi Mootha, associated scientist Zenon Grabarek at Harvard Medical School, and colleagues provide structural insights about the two proteins, thus explaining the gating mechanism of the uniporter. These findings will further guide disease research, especially in the area of neuromuscular disorder caused by MICU1 deficiency.

To learn more about research conducted at the Broad, visit, and keep an eye on