Nature Biotechnology

The ABC's of industry: a postdoc program provides a sneak peek into industry careers

Nature Biotechnology 28, 625 (2010). doi:10.1038/nbt0610-625

Authors: Adnan O Abu-Yousif, Erik C Hett, Ann M Skoczenski & Tayyaba Hasan

An innovative partnership allows local companies to educate postdocs about careers in industry.

People

Nature Biotechnology 28, 628 (2010). doi:10.1038/nbt0610-628

Rationalizing the development of live attenuated virus vaccines

Nature Biotechnology 28, 573 (2010). doi:10.1038/nbt.1635

Authors: Adam S Lauring, Jeremy O Jones & Raul Andino

Synthetic polymer coatings for long-term growth of human embryonic stem cells

Nature Biotechnology 28, 581 (2010). doi:10.1038/nbt.1631

Authors: Luis G Villa-Diaz, Himabindu Nandivada, Jun Ding, Naiara C Nogueira-de-Souza, Paul H Krebsbach, K Sue O'Shea, Joerg Lahann & Gary D Smith

We report a fully defined synthetic polymer coating, poly[2-(methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide] (PMEDSAH), which sustains long-term human embryonic stem (hES) cell growth in several different culture media, including commercially available defined media. The development of a standardized, controllable and sustainable culture matrix for hES cells is an essential step in elucidating mechanisms that control hES cell behavior and in optimizing conditions for biomedical applications of hES cells.

Identification of influenza A nucleoprotein as an antiviral target

Nature Biotechnology 28, 600 (2010). doi:10.1038/nbt.1638

Authors: Richard Y Kao, Dan Yang, Lai-Shan Lau, Wayne H W Tsui, Lihong Hu, Jun Dai, Mei-Po Chan, Che-Man Chan, Pui Wang, Bo-Jian Zheng, Jian Sun, Jian-Dong Huang, Jason Madar, Guanhua Chen, Honglin Chen, Yi Guan & Kwok-Yung Yuen

Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly, creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC50) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies.

Synthetic peptide-acrylate surfaces for long-term self-renewal and cardiomyocyte differentiation of human embryonic stem cells

Nature Biotechnology 28, 606 (2010). doi:10.1038/nbt.1629

Authors: Zara Melkoumian, Jennifer L Weber, David M Weber, Andrei G Fadeev, Yue Zhou, Paula Dolley-Sonneville, Jiwei Yang, Liqun Qiu, Catherine A Priest, Christopher Shogbon, Arthur W Martin, Jodelle Nelson, Peter West, James P Beltzer, Santona Pal & Ralph Brandenberger

Human embryonic stem cells (hESCs) have two properties of interest for the development of cell therapies: self-renewal and the potential to differentiate into all major lineages of somatic cells in the human body. Widespread clinical application of hESC-derived cells will require culture methods that are low-cost, robust, scalable and use chemically defined raw materials. Here we describe synthetic peptide-acrylate surfaces (PAS) that support self-renewal of hESCs in chemically defined, xeno-free medium. H1 and H7 hESCs were successfully maintained on PAS for over ten passages. Cell morphology and phenotypic marker expression were similar for cells cultured on PAS or Matrigel. Cells on PAS retained normal karyotype and pluripotency and were able to differentiate to functional cardiomyocytes on PAS. Finally, PAS were scaled up to large culture-vessel formats. Synthetic, xeno-free, scalable surfaces that support the self-renewal and differentiation of hESCs will be useful for both research purposes and development of cell therapies.

Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511

Nature Biotechnology 28, 611 (2010). doi:10.1038/nbt.1620

Authors: Sergey Rodin, Anna Domogatskaya, Susanne Ström, Emil M Hansson, Kenneth R Chien, José Inzunza, Outi Hovatta & Karl Tryggvason

We describe a system for culturing human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells on a recombinant form of human laminin-511, a component of the natural hES cell niche. The system is devoid of animal products and feeder cells and contains only one undefined component, human albumin. The hES cells self-renewed with normal karyotype for at least 4 months (20 passages), after which the cells could produce teratomas containing cell lineages of all three germ layers. When plated on laminin-511 in small clumps, hES cells spread out in a monolayer, maintaining cellular homogeneity with approximately 97% OCT4-positive cells. Adhesion of hES cells was dependent on α6β1 integrin. The use of homogeneous monolayer hES or iPS cell cultures provides more controllable conditions for the design of differentiation methods. This xeno-free and feeder-free system may be useful for the development of cell lineages for therapeutic purposes.

Ask your doctor

Nature Biotechnology 28, 644 (2010). doi:10.1038/bioe.2010.5

Authors: Jeffrey J Stewart, Jeron Eaves & Ben Bonifant

When seeking a licensing partner for a product in development, market projections and strategies require substantiation. This can be provided through physician interviews.

Comparative assessment of methods for aligning multiple genome sequences

Nature Biotechnology 28, 567 (2010). doi:10.1038/nbt.1637

Authors: Xiaoyu Chen & Martin Tompa

Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models

Nature Biotechnology 28, 585 (2010). doi:10.1038/nbt.1640

Authors: Mallika Singh, Anthony Lima, Rafael Molina, Patricia Hamilton, Anne C Clermont, Vidusha Devasthali, Jennifer D Thompson, Jason H Cheng, Hani Bou Reslan, Calvin C K Ho, Timothy C Cao, Chingwei V Lee, Michelle A Nannini, Germaine Fuh, Richard A D Carano, Hartmut Koeppen, Ron X Yu, William F Forrest, Gregory D Plowman & Leisa Johnson

Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations

Nature Biotechnology 28, 595 (2010). doi:10.1038/nbt.1641

Authors: David M Rissin, Cheuk W Kan, Todd G Campbell, Stuart C Howes, David R Fournier, Linan Song, Tomasz Piech, Purvish P Patel, Lei Chang, Andrew J Rivnak, Evan P Ferrell, Jeffrey D Randall, Gail K Provuncher, David R Walt & David C Duffy

The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or zero labeled target protein molecules per bead) with an enzymatic reporter capable of generating a fluorescent product. After isolating the beads in 50-fl reaction chambers designed to hold only a single bead, we used fluorescence imaging to detect single protein molecules. Our single-molecule enzyme-linked immunosorbent assay (digital ELISA) approach detected as few as ∼10–20 enzyme-labeled complexes in 100 μl of sample (∼10−19 M) and routinely allowed detection of clinically relevant proteins in serum at concentrations (<10−15 M) much lower than conventional ELISA. Digital ELISA detected prostate-specific antigen (PSA) in sera from patients who had undergone radical prostatectomy at concentrations as low as 14 fg/ml (0.4 fM).

Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe

Nature Biotechnology 28, 617 (2010). doi:10.1038/nbt.1628

Authors: Dong-Uk Kim, Jacqueline Hayles, Dongsup Kim, Valerie Wood, Han-Oh Park, Misun Won, Hyang-Sook Yoo, Trevor Duhig, Miyoung Nam, Georgia Palmer, Sangjo Han, Linda Jeffery, Seung-Tae Baek, Hyemi Lee, Young Sam Shim, Minho Lee, Lila Kim, Kyung-Sun Heo, Eun Joo Noh, Ah-Reum Lee, Young-Joo Jang, Kyung-Sook Chung, Shin-Jung Choi, Jo-Young Park, Youngwoo Park, Hwan Mook Kim, Song-Kyu Park, Hae-Joon Park, Eun-Jung Kang, Hyong Bai Kim, Hyun-Sam Kang, Hee-Moon Park, Kyunghoon Kim, Kiwon Song, Kyung Bin Song, Paul Nurse & Kwang-Lae Hoe

Sitting up and taking notice

Nature Biotechnology 28, 381 (2010). doi:10.1038/nbt0510-381

The sheer pace of discovery in genetics is placing companies that pursue an aggressive infringement strategy for gene patents increasingly at odds with innovation.

Biomarker-led adaptive trial blazes a trail in breast cancer

Nature Biotechnology 28, 383 (2010). doi:10.1038/nbt0510-383

Author: Malorye Allison

Biotechs adjust to new landscape as US healthcare reform takes off

Nature Biotechnology 28, 385 (2010). doi:10.1038/nbt0510-385

Author: Jeffrey L Fox

Genentech, UCSF discovery pact

Nature Biotechnology 28, 386 (2010). doi:10.1038/nbt0510-386

Author: Jennifer Rohn

Abbott outbids Biogen for Facet's multiple sclerosis antibody

Nature Biotechnology 28, 387 (2010). doi:10.1038/nbt0510-387

Author: Cormac Sheridan

FDA crackdown on Genzyme

Nature Biotechnology 28, 388 (2010). doi:10.1038/nbt0510-388

Author: Keith L Carson

Ariad's NF-κB blow

Nature Biotechnology 28, 389 (2010). doi:10.1038/nbt0510-389a

Author: Ken Garber

Orphan drug workshops

Nature Biotechnology 28, 389 (2010). doi:10.1038/nbt0510-389b

Author: Kirsten Dorans