Joining forces

Nature Biotechnology 27, 959 (2009). doi:10.1038/nbt1109-959

Similar to outsourcing in the corporate world, technology incubators are beginning to look beyond their own borders to find technology.

Nature Biotechnology 27, 971 (2009). doi:10.1038/nbt1109-971

Author: Charlotte Schubert

Steve Reed believes the organization he has founded has the potential to radically increase the developing world's access to vaccines for neglected diseases. The efforts of the Seattle-based Infectious Disease Research Institute (IDRI), which operates as a not-for-profit biotech company, may start to pay off during the H1N1 'swine' flu pandemic. IDRI developed an adjuvant to boost the effectiveness and supplies of flu vaccines and is making the technology available to vaccine manufacturers in developing nations. Charlotte Schubert talks to Reed about how IDRI, a 90-person operation with a $19 million annual budget, could have such a big impact.

Nature Biotechnology 27, 974 (2009). doi:10.1038/nbt1109-974

Author: Jeffrey L Fox

Agribusiness is taking another run at transgenic wheat after shelving its programs five years ago because of concerns from farmers, trade organizations and even state governments about market acceptance. Will there be a market this time? Jeffrey Fox investigates.

Nature Biotechnology 27, 977 (2009). doi:10.1038/nbt1109-977

Author: Sarah Webb

As the first commercial ventures are formed around induced pluripotent stem (iPS) cell research, who will have the freedom to operate commercially remains a big unknown. Sarah Webb reports.

Nature Biotechnology 27, 980 (2009). doi:10.1038/bioe.2009.9

Authors: Jeffrey J Stewart & Ben Bonifant

Holding the valuation high ground allows a biotech company to get the most value from potential partners. Here is how to establish and defend financial valuation.

Nature Biotechnology 27, 986 (2009). doi:10.1038/nbt1109-986

Author: Brady Huggett

Most drugs withdrawn from the market because of serious toxicities never make it back. But Biogen Idec succeeded in getting its multiple sclerosis (MS) drug Tysabri reintroduced in less than 16 months.

Nature Biotechnology 27, 987 (2009). doi:10.1038/nbt1109-987

Author: Saurabh Aggarwal

Despite the global economic slowdown, biologics managed single-digit growth in 2008, driven mainly by continued high growth in sales of antibodies and insulins. Novel biologics in development look promising, but crowding, pricing and reimbursement are emerging as longer-term concerns.

Nature Biotechnology 27, 994 (2009). doi:10.1038/nbt1109-994

Author: Charles Lawson

Patents may not establish clear property and use rights and this may promote biodiversity destruction and decline. What is needed are schemes for patents to suit conservation and sustainable-use objectives.

Nature Biotechnology 27, 997 (2009). doi:10.1038/nbt1109-997

Authors: Deepa Subramanyam & Robert Blelloch

As a differentiated cell proceeds toward the pluripotent state, markers turn on and off in an orderly fashion.

Nature Biotechnology 27, 998 (2009). doi:10.1038/nbt1109-998

Author: Ewen F Kirkness

Combining microdroplet PCR with flow-cell technologies provides a novel approach for sequencing thousands of genomic targets.

Nature Biotechnology 27, 999 (2009). doi:10.1038/nbt1109-999

Authors: Daniel E Zak & Alan Aderem

Large-scale perturbations unravel the complex networks of activated dendritic cells.

Nature Biotechnology 27, 1001 (2009). doi:10.1038/nbt1109-1001

Authors: Derek Y Chiang & Steven A McCarroll

Duplicated genomic regions are accurately resolved using an optimized algorithm for mapping reads from next-generation sequencers.

Nature Biotechnology 27, 1005 (2009). doi:10.1038/nbt.1584

Authors: Xiao-Song Wang, John R Prensner, Guoan Chen, Qi Cao, Bo Han, Saravana M Dhanasekaran, Rakesh Ponnala, Xuhong Cao, Sooryanarayana Varambally, Dafydd G Thomas, Thomas J Giordano, David G Beer, Nallasivam Palanisamy, Maureen A Sartor, Gilbert S Omenn & Arul M Chinnaiyan

Nature Biotechnology 27, 1025 (2009). doi:10.1038/nbt.1583

Authors: Ryan Tewhey, Jason B Warner, Masakazu Nakano, Brian Libby, Martina Medkova, Patricia H David, Steve K Kotsopoulos, Michael L Samuels, J Brian Hutchison, Jonathan W Larson, Eric J Topol, Michael P Weiner, Olivier Harismendy, Jeff Olson, Darren R Link & Kelly A Frazer

Nature Biotechnology 27, 1033 (2009). doi:10.1038/nbt.1580

Authors: Elayne M Chan, Sutheera Ratanasirintrawoot, In-Hyun Park, Philip D Manos, Yuin-Han Loh, Hongguang Huo, Justine D Miller, Odelya Hartung, Junsung Rho, Tan A Ince, George Q Daley & Thorsten M Schlaeger

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by enforced expression of transcription factors. Using serial live imaging of human fibroblasts undergoing reprogramming, we identified distinct colony types that morphologically resemble embryonic stem (ES) cells yet differ in molecular phenotype and differentiation potential. By analyzing expression of pluripotency markers, methylation at the OCT4 and NANOG promoters and differentiation into teratomas, we determined that only one colony type represents true iPS cells, whereas the others represent reprogramming intermediates. Proviral silencing and expression of TRA-1-60, DNMT3B and REX1 can be used to distinguish the fully reprogrammed state, whereas alkaline phosphatase, SSEA-4, GDF3, hTERT and NANOG are insufficient as markers. We also show that reprogramming using chemically defined medium favors formation of fully reprogrammed over partially reprogrammed colonies. Our data define molecular markers of the fully reprogrammed state and highlight the need for rigorous characterization and standardization of putative iPS cells.

Nature Biotechnology 27, 1038 (2009). doi:10.1038/nbt.1579

Authors: Susanne Pechhold, Melissa Stouffer, Gregory Walker, Ralph Martel, Bruce Seligmann, Yan Hang, Roland Stein, David M Harlan & Klaus Pechhold

Analyzing specialized cells in heterogeneous tissues is crucial for understanding organ function in health and disease. Thus far, however, there has been no convenient method for studying gene expression in cells purified by fluorescence-activated cell sorting (FACS) using intracellular markers. Here we show that the quantitative nuclease protection assay (qNPA) enables transcriptional analysis of intracytoplasmically stained cells sorted by FACS. Applying the method to mouse pancreatic islet–cell subsets, we detected both expected and unknown lineage-specific gene expression patterns. Some beta cells from pregnant animals were found to express Mafb, previously observed only in immature beta cells during embryonic development. The four 'housekeeping' genes tested were expressed in purified islet-cell subpopulations with a notable variability, dependent on both cell lineage and developmental stage. Application of qNPA to intracellularly stained, FACS-sorted cells should be broadly applicable to the analysis of gene expression in subpopulations of any heterogeneous tissue, including tumors.

Nature Biotechnology 27, 1043 (2009). doi:10.1038/nbt.1582

Authors: Byung-Kwan Cho, Karsten Zengler, Yu Qiu, Young Seoub Park, Eric M Knight, Christian L Barrett, Yuan Gao & Bernhard Ø Palsson

Nature Biotechnology 27, 1050 (2009). doi:10.1038/nbt.1581

Authors: Henrike Veith, Noel Southall, Ruili Huang, Tim James, Darren Fayne, Natalia Artemenko, Min Shen, James Inglese, Christopher P Austin, David G Lloyd & Douglas S Auld