Biosciences Area

Modular Ensembles of Enhancers Regulate Ihh, Developmental Gene Expression in Mice

Biosciences researchers Axel Visel (JGI/EGSB) and Marco Osterwalder (EGSB) contributed to a study, led by researchers at the Max Planck Institute for Molecular Genetics, in which targeted genome editing and a transgenic reporter assay were used to characterize elements regulating Ihh (encoding Indian hedgehog) in mice. Indian hedgehog is a mammalian signaling protein involved with the development and proliferation of cells in cartilage. In humans, copy number variants (CNVs) upstream of Ihh cause localized phenotypes including premature fusion of the sutures of the skull and malformation of the phalanges. The study, published in Nature Genetics, showed that in mice Ihh is regulated by modular ensembles of enhancers (with individual tissue specificities) that appear to act in an additive manner. Despite apparent redundancy and overlapping function of enhancers, these ensembles—in which the correct number of each enhancer is present—are necessary for precise spatiotemporal control of developmental gene expression.

Room Temperature XFEL Provides Clearest View Yet of Water Networks in Influenza M2 Proton Channel

Molecular Biophysics & Integrated Bioimaging (MBIB) Division scientists Aaron Brewster, Nicholas Sauter, and James Fraser were part of an international team led by William DeGrado at UCSF that used an X-ray free-electron laser (XFEL) source to visualize the arrangement of water molecules inside the influenza matrix 2 (M2) channel at room temperature. The M2 channel of influenza A is essential for the reproduction of the flu virus, making it a target for therapeutics, and it is also a model system for studying how protons are transported across a membrane bilayer. The XFEL method overcomes the limitations of previous crystallographic structures obtained using synchrotron radiation with cryocooling. While cryocooling helps to preserve crystals against rapid radiation damage, it imparts an artificially higher degree of order of the water molecules than structures obtained near room temperature. By using room temperature XFEL to study the M2 channel at various pH conditions, the researchers have gained a more accurate picture of the behavior of water molecules and their role in proton transport in these channels. The study was published in the Proceedings of the National Academy of Sciences.

Another Successful Year for Biotech Partners Interns at Biosciences Area

The Biosciences Area partnered once again with Biotech Partners to provide paid summer internships to high school students. This year six high school students worked side by side with Biosciences researchers across the Area’s laboratories. The mission of the non-profit Biotech Partners is to educate underserved youth in the Bay Area with personal, academic and professional development experiences that increase participation in higher education and access to fulfilling science careers.

Dub-seq Named a Finalist for R&D 100 Awards

A method for discovering gene function in microbes developed by Adam Arkin, Adam Deutschbauer, Vivek Mutalik, and Pavel Novichkov of the Environmental Genomics and Systems Biology division has been shortlisted for R&D Magazine’s 2017 R&D 100 Award. The technology, called Dual Barcoded Shotgun Expression Library Sequencing (Dub-seq), combines the shotgun expression library method and next generation sequencing method developed through the ENIGMA program. Now in its 55th year, the prestigious R&D 100 Awards program recognizes the most innovative inventions of the prior year. The winners will be announced and honored at a black-tie ceremony to be held this fall in conjunction with the annual R&D 100 Conference.

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