BiotecVisions 2013, April

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Editors: Judy Peng /jp; Adriana Kantcheva /ak; Lucie Kalvodova /lk


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Contributors: Danny Asling /da; Frédérique Belliard /fb; Allison Goldstein /ag; Fran Harding /fh; Meghana Hemphill /mh; Vera Koester /vek; Adrian Miller /am; Bill Mullen /bm; Anja Stephan /as; Gillian van Beest /gvb; Loes van de Pasch /lp; Nick Whitworth /nw

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April 2013

Cover story

Developing microbial cell factories using synthetic small regulatory RNAs

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An environmentally friendly way to produce desired chemicals and materials is by employing microorganisms turned chemical factories. Usually, naturally occurring microorganisms are inefficient producers, thus researchers commonly use the method of metabolic engineering to increase yield and reduce production costs. Up to now, probing a microorganism's genome for suitable target genes through gene amplification and knockout is considered a daunting task. Researchers led by Prof. Sang Yup Lee (KAIST, Korea) suggest a simple strategy to identify genes for knock-out or knock-down experiments by utilizing synthetic small regulatory RNA (srRNA). srRNAs can be used to fine-tune the expression of multiple genes at the level of translation. As a proof of concept, Na et al. engineered an Escherichia coli strain to produce the amino acid tyrosine, which is used as a medication for stress relieve, as well as in the food industry. The researchers also improved production of cadaverine, used in making nylon, by another, already engineered E. coli strain. Using srRNAs is a powerful, yet simple technique that can be employed on a wide variety of microorganisms to turn them into potent cellular factories. /ak

Na et al., Nat. Biotechnol. 2013

Top biotech developments

Each year, the experts on the World Economic Forum's Council on Biotechnology meet in Davos to discuss and evaluate the latest trends in biotechnology and the implications of these technologies. The top 5 developments according to the experts:

1. Bio-based sustainable production of chemicals, energy, fuels and materials

Continued depletion of fossil fuels has been the norm in the past century – in order to achieve sustainable development, a carbon-neutral solution is needed. Biotechnology enables the production of the much needed energy, chemicals and materials in a potentially sustainable, renewable manner;

2. Sustainable food production

While genetic modification is a controversial topic, it cannot be denied that it has improved agricultural productivity. With careful control and management, these crops can lower pesticide use, improve productivity on marginal land and reduce soil erosion;

3. Sea water-based bio-processes

The ocean is one of our under tapped-resources – with 70% of the earth's surface covered by water, the potential is immense. Examples include halliophic bacteria that can be engineered to produce useful chemicals and materials, as well as ocean agriculture based on macroalgae and microalgae;

4. Zero waste bio-processing

“Zero waste” entails processing of waste streams into valuable chemicals and fuels. By-products from bioprocessing, such as methane and waste heat, can all be turned into valuable products;

5. CO2 as a raw material

Researchers are working on ways of converting C02 and carbon into energy, fuels, chemicals and new materials – paving the way for solutions to the growing threat of rising CO2 levels.

This is a synopsis of the World Economic Forum blog post, by Prof. Sang Yup Lee, Chair of the World Economic Forum's Global Agenda Council on Biotechnology. For the remainder of the developments in the top 10 list, refer to the original post at:

Getting Published

Optimizing your article for search engines

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More and more researchers these days use Google or other search engines to look for scientific publications – while high usage does not necessarily correlate with citations, high citations almost does not happen without high usage. Furthermore, as the h-index (more on that topic in a later article in the column) becomes a more frequently used measure of success for researchers, you too should care about how your articles are being discovered through search engines.

Some tips for “optimizing” the discoverability of your article via search engines:

Step 1: Construct a clear, descriptive title

The title is the most important part of your article – not only for readers but also for search engines. Search engines place most weighting on the words used in the title. Imaging that you are looking for an article, which keywords would you use? Put these into your title, and put them towards the beginning of the title – words at the beginning also have more value than words at the end.

Step 2: Reiterate key phrases

After the title, the next most important part is the abstract. Keywords from the title should be reiterated where possible. Avoid the use of pronouns such as “it”, “they”, instead, use the actual term itself. Not only does it make your article more understandable to the readers, they also help improve the search engine ranking of your article. Note: repetition within context and reason is key. Unnecessary repetition is likely to lead to search engines rejecting your page.

Take home message:

Search engines attempt to provide the most relevant content to its users. So when writing your article, think about how a reader might perceive your article. Relevant keywords in the title and abstract are, at the end of the day, what the readers are looking for.

This is a summary of “Optimizing your article for search engines” from Wiley's Author Services site.

Deep eutectic solvents

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Deep eutectic solvents are novel media with properties similar to ionic liquids but providing some additional advantages such as a lower cost and environmental impact. These solvents result from the association of an organic salt (ammonium or phosphonium) with a hydrogen-bond donor such as alcohol, acid or amide. In European Journal of Lipid Science and Technology, Durand et al. review the key characteristics and potential applications of deep eutectic solvents with a special focus on lipase-catalyzed reactions including hydrolysis, aminolysis or alcoholysis. /lk

Durand et al., Eur. J. Lipid Sci. Technol. 2013

Trans-free margarines

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In Lipid Technology, Pande and Akoh present a Feature article on trans fats and enzymatic modification of lipids for producing trans-free margarines. Enzymatic transesterification is a possible alternative to partial hydrogenation to obtain trans-free margarines with desirable physical and functional properties. /lk

Pande and Akoh, Eur. J. Lipid Sci. Technol. 2013

Increasing the potency of “natural product” medicines through synergistic combination

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Plant extracts, herbal medicines and other natural products (NPs) are widely used in complementary medicine and now are increasingly of interest as new sources of pharmacologically active agents. Typically, NPs are prescribed in combinations that are personalized for individual patients. An analysis conducted by researchers from the National University of Singapore and Tsinghua University compared the activity of synthetic drugs and NPs traditionally used to treat cancer and bacterial infection. NPs tended to require higher doses to gain the same effect as synthetically derived drugs. By selecting NPs of sufficient potency and in correct combination, however, traditional remedies approached the level of efficacy shown by synthetic drug treatments. Intriguingly, individual genetic variation is suggested to be more influential to the outcome of NP-based therapy than synthetic drug treatments. /fh

Qin et al., PloS One, 2012

Faster is better: Evolution speeds up protein folding

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Across the range of naturally occurring protein structures, the time required for protein folding varies from microseconds to hours. This deviation reflects the structural diversity of protein forms that have evolved since their appearance 3.8 billion years ago. New work published in the journal PLoS Comput. Biol examines how the rate of protein folding has changed through time. Estimated folding times for 92000 proteins derived from 989 genomes were mapped onto an evolutionary timeline. An overall increase in folding speed was observed over time. Faster folding is hypothesized to confer an advantage by increasing protein availability to the cell and preventing aggregation of misfolded proteins. Interestingly, folding time for β-fold structures have tended to move against this general trend, increasing during the last 1.5 billion years. /fh

Debès et al., PLoS Comput. Biol. 9

Successful printing of human embryonic stem cells

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The fabrication of three dimensional artificial tissues requires a means to place cells into precise and reproducible patterns. Collaboration between Heriot-Watt University and Roslin Biocentre has resulted in a way to print human embryonic stem cells (hESCs) into 3D aggregates. hESCs are highly sensitive to physical manipulation and require the retention of extracellular matrix on the cell surface for cell survival. A valve based printer, in which cell deposition is controlled by pneumatic pressure and the opening and closing of a microvalve, is gentle enough to pattern hESCs into a programmed pattern without losing viability. The rapid throughput made possible by automated printing facilitates the incorporation of hESC derived tissue aggregates to drug discovery and toxicity testing processes, reducing reliance on animal models. In the long term, this method of cell printing could also be used to generate artificial organs for transplantation. /fh

Faulkner-Jones et al., Biofabrication, 2013

The health benefits of green tea

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Green tea is a popular drink worldwide, and its consumption has been suggested to prevent the development of a variety of diseases, including diabetes, hypertension, cancer and cardiovascular diseases. Its effects are attributed to its abundant and biologically active catechin, epigallocatechin-3-gallate (EGCG), which has anti-oxidative and anti-inflammatory effects. Atherosclerosis is a leading cause of mortality and morbidity in western countries. Studies have indicated that chronic inflammatory responses and oxidative stress conditions for example chronic infection with a periodontal pathogen, such as Porphyromonas gingivalis, is associated with an increased risk of atherosclerosis. This translational research study demonstrates the ability of EGCG, a polyphenol extract from green tea, to protect against P. gingivalis-induced atherosclerosis. /gvb

Yu Cai et al., Pathogens and Disease, 2012

Zinc finger protein Gsf1 regulates Gsf2-dependent flocculation in fission yeast

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Flocculation is a process by which cells form aggregates. Fission yeast flocculates by induction of the flocculin gene gsf2+, which is controlled by the positive regulator mbx2+. In this study, the authors have identified a novel gene named gsf1+ that represses gsf2+- and mbx2+-dependent flocculation. Gsf1+ encodes a 547 amino acid zinc finger protein and localizes in the nucleus, consistent with a role of a transcription factor. Deletion of gsf1+ results in flocculation, despite high expression of gsf2+ and mbx2+. The gsf1+ deletion mutant was also found to be sensitive to CaCl2, KCl, HU, and TBZ, supporting a role of gsf1+ in other functions unrelated to flocculation. These findings help to understand the transcriptional regulatory network of flocculation in fission yeast. /fb

Matsuzawa et al., FEMS Yeast Research, 2013

Functional gene surveys from ocean drilling expeditions

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The subsea floor is inhabited by microbes, which perform key microbial processes, such as sulfate reduction and methanogenesis. In the past decade, several ocean drilling expeditions have been performed, which has given great insight into the distribution and diversity of these microbial communities and their contribution to specific metabolic reactions. This review gives an overview of the functional genes of metabolic and biosynthetic processes that were derived from these studies. The study of these genes, using a highly interdisciplinary approach from the fields of microbial ecology, molecular biology, microbiology, and geochemistry, will ultimately lead to a better understanding of the energy sources, biosynthetic pathways, and survival strategies of microbes in the subsea floor. /lp

Lever, FEMS Microbiology Ecology, 2013

Immunoglobulin domains in enterobacteria: applications in antibody technologies

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This review describes the proteins containing immunoglobulin (Ig)-like domains in Escherichia coli and other enterobacteria, reporting their structural and functional properties, protein folding, and diverse biological roles. The authors also review the expression of heterologous Ig domains in E. coli, focusing on the current technologies for expression and selection of small antibody fragments and full-length Ig molecules in this bacterium, given its biotechnological significance for the development of therapeutic antibodies. The authors conclude that a better understanding of these processes will not only provide a rational basis for the design of new anti-microbial compounds to combat infection, but will help to improve current expression systems. /gvb

Bodelón, et al., FEMS Microbiology Reviews, 2013

Mycotoxin biosynthesis

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Mycotoxins, secondary metabolites produced by fungi on foods and foodstuffs, pose significant food safety risks and health hazards and ultimately limit the marketability of grain supply worldwide. This review focusses on the three key mycotoxins that have enormous impact on the quality of grain: aflatoxins, fumonisins, and trichothecenes. /gvb

Woloshuk and Shim, FEMS Microbiology Reviews, 2013

Straw: Future Bioenergy Pathway?

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Straw is the most abundant biomass residue in Europe and its use for energy purposes is promoted on the premise of high greenhouse gas savings; this assumption has delayed the study of sustainability of straw-fired systems on a broader sense and the literature on the topic is almost absent. In this study, the authors use data from specific literature and emissions inventories to model a number of straw pathways. The results show that electricity from straw-fired power plants can indeed realize high greenhouse gas savings compared both with existing coal plants and with the European electricity mix, generating savings in the range of 70–94%. /nw

Giuntoli et al., GCB Bioenergy., 2012

Creating physiological conditions outside the body

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Inside the human body, tissues and organs are embedded into a complex macro-environment that determines the form and function of an organ. Nutrients and oxygen are supplied to the organ by the pulsatile blood flow created by the beating heart. On the other hand, artificial tissues, made in the laboratory, are usually simply submerged in growth media, where they miss vital stimuli, and the size of engineered tissues is limited, due to the lack of a perfused vasculature. In this issue, Groeber et al., (Institute for Interfacial Engineering, University of Stuttgart, Germany) describe the development of a device that is capable of creating a suitable macro-environment for engineered vascularized tissues, which uses a sophisticated fluidic system to provide an artificial blood stream. Vascularized skin equivalents have a broad spectrum of application for use as advanced wound dressings or as test systems for the replacement of animal experiments. /ak

Groeber et al., Biotechnol. J. 2013

3D elastic fiber dermal construct as a tool for tissue engineering

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Elastin is one of the most important fiber proteins in connective tissue. It is responsible for elasticity of tissues like skin, lung, and vessel walls. The loss of elastin can cause diseases like Marfan Syndrome or Cutis Laxa. In mammals, the levels of elastin production are highest only during two points of the organism's lifetime – embryogenesis and wound healing. In this issue, Sommer et al. (Beiersdorf AG, Hamburg, Germany) present and fully characterize a 3D elastic fiber dermal construct based on growth factor (TGF-β1) stimulation for bioengineering purposes. Characterization of the construct was conducted using various imaging techniques (multiphoton, confocal and electron microscopy, and nanorods) combined with cross-link analyses. This tissue-engineered dermal construct may prove to be an effective template for the development of medicinal approaches in regenerative soft skin tissue reconstruction through TGF-β1 induction. /ak

Sommer et al., Biotechnol. J. 2013

Non-invasive molecular fingerprinting of cells and tissues

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Non-invasive optical methods have become more and more important in the field of biomedical research and diagnostics. During the last decade, Raman spectroscopy has emerged as one of the most interesting laser-based technologies for non-contact diagnosis. Raman spectroscopy uses inelastic light scattering to provide sample-specific molecular information. Such spectral information has repeatedly been shown to be valuable for the characterization and analysis of a broad-spectrum of biological specimens from small microorganism to whole tissue biopsies. In this issue, Brauchle and Schenke-Layland (Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany) give an overview of the biomedical, in vitro applications of Raman spectroscopy. This review recaps recent progress in Raman spectral identification of microorganisms and discusses more complex spectral analysis in mammalian cell cultures and extracellular matrix components. /ak

Brauchle and Schenke-Layland, Biotechnol. J. 2013

IUBMB events

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8th General Meeting of the International Proteolysis Society

Cape Town, South Africa, 20–24 October 2013

Contact: Prof. E. Sturrock, Division of Medical Biochemistry & IIDMM, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa, E-mail:

Synchrotron Radiation Techniques and Nanotechnology

A Synergic Approach to Life Sciences and Medicine

Cape Town, South Africa, 11–29 November 2013

Contact: Silvia OnestiStrada Statale 12, km 1635 in Area Science Park, 34149 Basovizza, Trieste, Italy, E-mail:

Oesophageal Cancer in Africa: The scientific, clinical and societal challenge

Durban, South Africa, 25-26 November 2013

Contact: Prof. Christopher Mathew, Department Medical & Molecular Genetics, 8th floor Tower Wing, Guy's Hospital, London SE1 9RT, United Kingdom, E-mail:


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DNA-based programing of quantum dot properties

QD properties including size, morphology, dispersity, emission maximum, and quantum yield are highly dependent on the sequences and structures of nucleic acids used for synthesis. This strategy provides a novel facile means of constructing compact, stable, and biofunctionalized QDs in one step for biosensing, bioimaging, and self-assembly.

Ma and Kelley, WIREs Nanomed Nanobiotechnol. 2013.

Bioimage informatics for understanding spatiotemporal dynamics of cellular processes

Bioimage informatics, or the computational analysis and understanding of recorded image data, is needed to infer systems-level molecular mechanisms that underlie spatiotemporal cell dynamics. This is crucial for comprehending complex interactions among the molecular complexes involved. /mh

Yang, WIREs Syst Biol Med 2013.

Using mutants, knockdowns, and transgenesis to investigate gene function in Drosophila

The sophisticated genetic techniques available in Drosophila are largely responsible for its success as a model organism. This review considers the ever-increasing repertoire of approaches for perturbing the functions of specific genes in flies.

St Johnston, WIREs Dev Biol 2012.

Machine learning methods for predicting tumor response in lung cancer

Despite the effectiveness of radiotherapy against many cancers, it fails in most lung cancer patients. This review discusses genetic and signaling pathways that modulate tumor response to radiotherapy in lung cancer as a case study of data mining in the challenging cancer problem.

El Naqa, WIREs Data Mining Knowl Discov. 2012

Current Protocols

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Using membrane vesicle for drug safety assessment

The use of plasma membrane vesicles offers a rapid and reliable means for screening drug candidates for their effects on transporter function in hepatocytes, and thus their potential for causing drug-induced liver injury. This is done with plasma membrane vesicles that overexpress the bile salt export pump (BSEP) or multidrug resistance – associated protein 2, 3, or 4 (MRP2-4) with an in vitro vacuum filtration system. Researchers from Amgen, Inc. use a model that influences the drug development process at an early stage and provide rapid feedback regarding the selection of compounds for advancement to in vivo safety evaluations. A detailed protocol for the high-throughput assessment of ABC transporter function is provided, including specific recommendations for curve-fitting to help ensure consistent results. /bm

Staden et al. Curr. Protoc. Toxicol. 2012

G-Quadruplexes and their interactions with drugs

Although DNA is most widely known for its ability to store and pass along genetic information, the discovery of G-quadruplex structures has illuminated a new role for DNA in biology. DNA G-quadruplexes are four-stranded globular nucleic acid secondary structures formed in specific G-rich sequences with biological significance, such as human telomeres and oncogene promoters. The unimolecular DNA G-quadruplexes can readily form in solution under physiological conditions and are considered to be the most biologically relevant. Available structural data show a great conformational diversity of unimolecular G-quadruplexes, which are amenable to small-molecule drug targeting. The authors discuss the relationships between sequence, structure, and stability of unimolecular DNA G-quadruplexes, as well as the recent progress on interactions with small-molecule compounds and insights into rational design of G-quadruplex-interactive molecules.

Chen and Yang. Curr. Protoc. Nucleic Acid Chem. 2012.


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Staying competitive in today's economic climate

Taking a side-step from our usual interview format, this month, we highlight the need to maintain adaptability in order to meet the demands of today's rapidly changing market.

In a blog post on the Wiley Job Network, Miriam Salpeter, owner of Keppie Careers, suggests the following 5 key steps to maintain competitiveness in a rapid change, slow growth economy:

Research constantly: the amount of information available on the web these days is almost endless – there is therefore no excuse not to know the latest trends in your industry and what employers are looking for – a quick glance at job sites will update you on employers' requirements, which leads us to the next point:

Continuing education: once you know what skill sets you might be missing, it's easier to go about updating your expertise. These may be in the form of formal training programs to picking up the right book. Social media is another good place for staying up-to-date with industry trends

Identify your transferable skills: in a rapidly changing environment, it is possible and likely that there may be no positions available in what you have been trained to do. Examine what skill sets you have to offer to “other” industries and whether you could imagine a fulfilling career in these industries.

Don't look like a dinosaur: if you have not applied for a job for a while, not only are the contents of your CV out of date, it is also possible that how people apply for a job has changed – be sure to know what the industry norm is.

Network and use social media tools: social media is becoming more and more important in our professional networks. According to research, most companies in the U.S. (92%) use social networks in their recruitment process in 2012.

For full article, go to Wiley Job Network:

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Biotech on the web

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No bread without chemistry

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Transformation of ripe ears of grain into a fragrant, aromatic bread borders on the miraculous. It is an accomplishment achievable only with the help of many hands: from those of the people responsible for the grain hybrids, through the farmer, to the miller, and finally the baker. Behind such “miracles” often lies a hefty amount of chemistry. A truly unique bread paradise is Germany, with its host of numerous regional bread specialties. Klaus Roth, Berlin, Germany, starts in the first of three parts to reveal the secrets involved in transforming ripe ears of grain into a fragrant, aromatic bread. Perhaps with some surprise we note the numerous chemical processes that unfold before us. /vek

Roth, ChemViews magazine 2013.

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Nanoscale biomaterials: Cutting edge bone therapy

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New work seeks to control the growth mechanisms of calcium phosphate nanobiomaterials of monetite.

Startups in materials: An interview with Shenda Baker

An interview with Shenda Baker, former university professor turned startup founder at biomedical polymers company Synedgen.


Downstream Industrial Biotechnology: Recovery and Purification

(From the renowned Encyclopedia of Industrial Biotechnology)

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Edited by Michael C. Flickinger

ISBN: 978-1-1181-3124-4

Hardcover | 872 pages | March 2013

Introductory Price, valid until 30th April 2013: $250.00 | £170.00 | €219.00

Thereafter: $395.00 | £265.00 | €342.00

Stem Cells: From Biology to Therapy

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Edited by Robert A. Meyers

This third book in the Current Topics in Molecular Cell Biology and Molecular Medicine Series contains a careful selection of new and updated, high-quality articles from the well-known Meyer's Encyclopedia, describing new perspectives in stem cell research. The 40+ chapters are divided into four sections: Basic Biology, Stem Cells and Disease, Stem Cell Therapy Approaches, and Laboratory Methods, with the authors chosen from among the leaders in their respective fields.

Liposomes in Nanomedicine

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A Curated Collection from eLS, WIREs, and Current Protocols

Perfect for students or interdisciplinary collaborators, this e-book collection provides the reader with an excellent introduction to some of the many ways in which liposomes can be labeled and used in both diagnostic and therapeutic applications.