BiotecVisions 2013, January

Special Edition: Methods

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Editors: Judy Peng /jp; Lucie Kalvodova /lk

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Contributors: Fran Harding /fh; Joanna Cipolla /jc; Barbara Janssens /bj; Frédérique Belliard /fb; Meghana Hemphill /mh; Mia Ricci /mr; Loes van de Pasch /lp; Anja Gaugel /ag

January 2013

Welcome to IUBMB

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BiotecVisions is pleased to announce our formal collaboration with the International Union of Biochemistry and Molecular Biology (IUBMB). As of January 2013, Biotecvisions will be published in liaison with the Union, aiming to further promote IUBMB news and events, and biotechnology research from the IUBMB journals published by Wiley, including, Biotechnology and Applied Biochemistry, Biochemistry and Molecular Biology Education, BioFactors and IUBMB Life.

IUBMB was founded in 1955 and unites biochemists and molecular biologists from some 77 member countries.

Through the publication of several prominent journals and hosting of important workshops and conferences, IUBMB plays an active role in promoting education in the field of biochemistry and molecular biology, (including biotechnology), especially in countries that aim at a higher scientific development. Toward this goal, IUBMB offers short-term fellowships and organizes advanced schools in countries such as China, India, Brazil, Iran and South Africa.

BiotecVisions has already worked with IUBMB journals, most notably the “Journal Spotlight” in the October 2012 issue, in which the two new Editors-in-Chief, Prof. Gianfranco Gilardi (University of Torino, Torino, Italy) and Prof. Jian-Jiang Zhong shared with us their vision of the future of the Journal. This formal agreement will ensure that BiotecVisions continues to share IUBMB research and news with our audience and also bring BiotecVisions to the attention of IUBMB members.

Coverage of IUBMB news and research in BiotecVisions will take the form of our usual article summaries and also a feature box containing IUBMB news and events when appropriate.

We look forward to bringing the most exciting research news from IUBMB to our readers!

See also recent article

Getting Published

Professional language editing before peer-review?

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I am often asked at conferences by non-native English speakers, whether they should send their articles for professional language editing prior to submitting their manuscripts to a journal.

As an editor facilitating the peer-review process, my answer to the question is yes and no. There are several shades of grey when it comes to how the language of a paper affects its chances of successfully going through peer-review, let's discuss this from the language quality perspective:

Incomprehensibly bad: sometimes the language of a paper is so bad that even a professional editor is unable to decipher what the authors are trying to say. If the authors are lucky, the paper will be sent back, requesting language editing prior to peer-review; if the authors are not lucky, the paper may be rejected by the editor without peer-review.

Poor: this is actually the worst case scenario – a tolerant and patient editor may work hard to understand the science and send it out for peer-review, only to be received by reviewers who are neither as tolerant nor patient and recommend rejection of the paper as they cannot easily understand the work.

Clearly, neither situation is desirable. To avoid the unnecessary frustration of receiving rejection letters, my answer to the question is to solicit the help of a friend or colleague who has excellent scientific English skills and is familiar with your scientific area, and therefore able to understand whether you have communicated the message effectively.

Such a friend is not always easy to come by, the next-best option would be language editing by a professional company – but not just any company. We often receive manuscripts that are accompanied by a certificate stating that the manuscript has been professionally edited – ironically, sometimes the results are quite disappointing. If you wish to use a professional company, select one recommended by a major publisher, who is likely to have more experience and provide better service. /jp

Judy Peng is Managing Editor of Biotechnology Journal

Continuous purification for the universal biomanufacturing platform

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The biotechnology industry currently uses two distinct manufacturing platforms for production of therapeutic proteins: fed batch processes for relatively stable proteins, such as monoclonal antibodies, and perfusion processes for relatively unstable proteins, e.g. recombinant enzymes. The emerging business drivers of cost, speed and flexibility in biotech require a universal biomanufacturing platform. In this issue, Godawat et al. (Genzyme – A Sanofi Company, Framingham, MA, USA) discuss continuous capture purification using periodic counter current chromatography (PCC) as part of a universal, integrated and continuous biomanufacturing platform. Specifically, a theoretical approach towards designing a continuous capture operation using PCC is shown and then applied to mAb and non-mAb proteins. The new platform offers several advantages, including low capital investment with smaller facility foot-print, better process economics by increased resin utilization, steady state operation, minimal scale-up and hold times, as well as fewer and streamlined unit operations. [1]

YeastIP: A database for identification and phylogeny of Saccharomycotina yeasts

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The authors present a searchable multigene database, YeastIP, that will quickly allow the identification of ascomycete yeasts. YeastIP has been designed to guide the user through all the steps starting from the choice of well-adapted markers and species, to the authentication or reconstruction of phylogeny. It contains useful tools for deducing the phylogenetic position of a strain/species on the basis of the concatenation of the sequences of several genes. YeastIP is a database devoted to yeast identification and phylogeny by experienced taxonomists, and can also be exploited by non-specialists. YeastIP facilitates multigenic analysis to encourage good practice in ascomycetous yeast phylogeny. This database should give results much more quickly than a search of GenBank. /fb [2]

Characterization of picoplankton by flow cytometry

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Flow cytometric sorting has been successfully employed to taxonomically affiliate a conspicuous group of red autofluorescent picoplankton in surface waters of the South Atlantic Ocean. Picoeukaryotes play a major role in CO2 fixation in the ocean, however, their diversity and distribution patterns remain poorly understood, partly because of their low abundance and methodological constraints. The authors have used catalysed reporter deposition fluorescence in situ hybridization to sort an uncharacterized group of picoplankton cells, which were identified to be affiliated with the Mamiellales clade II. The cells were further morphologically characterized by electron microscopy and were shown to have a simple cell morphology. This demonstrates that flow cytometry is a powerful method for the characterization of lowly abundant populations of picoplankton./lp [3]

Heart on a chip

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The heart is particularly sensitive to injury because of its low regenerative capacity. A microscale tissue array, described in PLoS One, supports the high throughput screening of cardiac cell response to soluble, surface immobilised and electrical stimuli, leading to new opportunities to probe cardiac injury and regeneration. The coupling of a tissue microarray with a microfluidics system enables soluble molecules to be delivered to specific spots on the array. The capture of data describing cardiac contractile function for each array spot is a unique feature of this work. This platform allows 400 parallel experimental replicates to be examined simultaneously. Its potential for use in toxicology was demonstrated by titration of cell response against hydrogen peroxide concentration, a model of oxidative stress that occurs in cardiac disease states. /fh [4]

Generating anti-viral monoclonal antibodies directly from human serum

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Proof of concept for a technique to rapidly generate monoclonal antibodies directly from human serum has been reported in Nature Biotechnology. High affinity hepatitis B virus-specific antibodies were derived directly from the circulation of a donor vaccinated against the virus. Antibodies with desired properties were first enriched using immunomagnetic beads. The enriched pool was analysed by liquid chromatography tandem mass spectrometry by matching to a reference database of antibody variable regions, produced by sequencing B-cells derived from the same donor after vaccination. Promising light and heavy chain sequences were then paired combinatorially, expressed and screened for maximum reactivity against the viral antigen. A similar strategy was used to clone a neutralising monoclonal antibody against human cytomegalovirus from a naturally infected individual./fh [5]�

Comparison of two methods for designing calorimeters using stirred tank reactors

Calorimetry is a robust method for online monitoring and controlling bioprocesses in stirred tank reactors. Up to now, reactor calorimeters have not been optimally constructed for pilot scale applications. Thus, the objective of this paper by Lars Regestein et. al. is to compare two different ways for designing reactor calorimeters and validate them. The “heat capacity” method based on the mass flow of the cooling liquid in the jacket was compared with the “heat transfer” method based on the heat transfer coefficient continuously measured in the cultivation of Escherichia coli VH33 in a 50 L stirred tank reactor. It was found that the values of the “heat transfer” method agreed very well with the calculated values from the oxygen consumption. By contrast, the curve of the “heat capacity” method deviated from that of the oxygen consumption calculated with the oxycaloric equivalent. In conclusion, the “heat transfer” method has been proven to have a higher degree of validity than the “heat capacity” method. Thus, the authors found that it is a better and more robust means to measure heat generation of fermentations in stirred tank bioreactors on a pilot scale. [6]

Statistical vs. Stochastic experimental design: An experimental comparison on the example of protein refolding

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Optimization of experimental problems is a challenging task in both engineering and science. In principle, two different design of experiments (DOE) strategies exist: statistical and stochastic methods. Both aim to efficiently and precisely identify optimal solutions inside the problem-specific search space. In this article, Bernd Anselment and coworkers evaluate and compare both strategies on the same experimental problem, the optimization of the refolding conditions of the lipase from Thermomyces lanuginosus with 26 variables under study. This study highlighted the limits of the classic two-step statistical DOE. [7]

Genome modifications in plant cells by custom-made restriction enzymes

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Genome editing, i.e. the ability to mutagenize, insert, delete and replace sequences, in living cells is a powerful and highly desirable method that could potentially revolutionize plant basic research and applied biotechnology. Various research groups from academia and industry are in a race to devise methods and develop tools that will enable not only site-specific mutagenesis but also controlled foreign DNA integration and replacement of native and transgene sequences by foreign DNA, in living plant cells. In this review, the authors discuss the principles and tools for restriction enzyme-mediated gene targeting in plant cells, as well as their current and prospective use for gene targeting in model and crop plants. /jc [8]

Life-cycle assessment of local feedstock supply scenarios to compare candidate biomass sources

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The use of life cycle assessment (LCA) as a comprehensive tool to assess environmental impacts of bioenergies is recommended. Nevertheless, several methodological points remain under debate, particularly regarding the feedstock production step, which is a key stage of bioenergy chains. The present work focuses on field emissions during feedstock production, improving assessment methods by the use of process-based models. To do so, a real bioenergy chain, the local feedstock supply for a boiler located in northern France, was studied. Six feedstock supply scenarios were also compared. The study aimed to test a new LCA methodology for agricultural chains by integrating local characteristics (such as climate, soil, and crop management data) and using models to estimate field dynamics of pesticide emissions and soil organic carbon (SOC). This study demonstrated the relevance of integrating simulation models using local data in agricultural LCAs, especially for dynamics of SOC and pesticide from fields. [9]

Bio-based production of C2–C6 platform chemicals

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Platform chemicals composed of 2–6 carbons derived from fossil resources are used as important precursors for making a variety of chemicals and materials, including solvents, fuels, polymers, pharmaceuticals, perfumes, and foods. Due to concerns regarding our environment and the limited nature of fossil resources, however, increasing interest has focused on the development of sustainable technologies for producing these platform chemicals from renewable resources. The techniques and strategies for developing microbial strains for chemicals production have advanced rapidly, and it is becoming feasible to develop microbes for producing additional types of chemicals, including non-natural molecules. In this study, Sang Yup Lee and coworkers review the current status of the bio-based production of major C2–C6 platform chemicals, focusing on the microbial production of platform chemicals that have been used for the production of chemical intermediates, building block compounds, and polymers. [10]

Pesticide detection in palm oil

In European Journal of Lipid Science and Technology , Yeoh and Chong report an LC-MSMS method for acetamiprid residue detection and quantification in crude palm oil. Acetamiprid is a candidate pesticide for use in oil pam plantations to control bagworms and leaf eating caterpillars. /lk [11]

Authenticating wild salmon

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The production of farmed Atlantic salmon has increased remarkably over the last two decades. However, wild salmon is often perceived by consumers as superior in terms of quality and nutritional properties and is sold at a considerably higher price -which might tempt producers to mislabel farmed salmon and sell farmed fish as wild fish. In Lipid Technology, Capuano et al. describe a method to predict wild salmon authenticity using 1H-NMR and multivariate statistics. /lk [13]

Special issues

ELECTROPHORESIS: Next Generation Sequencing and Genotyping

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It is rare to have a front row seat to watch an entire field emerge, grow, and begin to mature within the span of a decade. This is one of the most exciting things about the field of “Next Generation Sequencing”, and it is in this spirit that ELECTROPHORESIS presents an outstanding collection of papers dedicated to this topic. We have assembled a diverse mix of reviews, technology-focused, and application-oriented papers that convey both the current state of the field and a glimpse of future directions. The review and technology-focused contributions are weighted toward nanopore-based methods, reflecting the rapid pace of recent progress in this area. The application-oriented papers cover a broader range of topics, but one aspect that stands out is the capability to study genetic variation.

Separation Science: Enabling technology in biotech

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The special issue on biotechnology is focused on separation science in industrial biotechnology. In order to achieve pharmaceutical quality products, several bioseparation steps are necessary, usually in the form of a three-step chromatographic separation involving capture, purification, and polishing, These steps must ensure complete removal of host cell proteins and nucleic acids, endotoxins, and viruses.

The present special issue documents the important role separations play in this field.


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Don't miss these 17 original research articles from the Journal of Chemical Technology and Biotechnology reflecting recent developments and novel strategies in the areas of environmental pollution mitigation and waste valorisation.

The articles were first presented at the 5th European Bioremediation Conference in Greece.

Emerging gel-free separation and detection methods

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Analysis of biological samples comprising complex mixtures of proteins, their isoforms and post-translational modifications is the core of proteomics. This Special Issue of PROTEOMICS, focuses on the latest directions and emerging gel-free technologies, which have the potential to provide more sensitive and efficient protein separation, detection and identification.

New and emerging technologies for clinical proteomics

The successful analysis and characterization of clinical samples, which consist of complex mixtures of proteins, often with a large degree of biological variability, requires the efficient and reproducible protein detection and quantitative methods. This Focus Issue of PROTEOMICS – Clinical Applications addresses several technical improvements, emerging technologies and new directions that have the potential to lead to improved protein identification and characterization, specifically for human biological samples.

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RNA biology in a test tube – an overview of in vitro systems/assays

Progress in the study of pre-mRNA processing, spliceosomes, and transcription has largely relied on traditional in vitro methods. Cell-free assays have also been applied to newly discovered pathways such as those involving small RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs). New techniques, such as single-molecule studies, are continuously being established, providing new and important insights into the field. [14]

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In situ labeling and imaging of endogenous neural stem cell proliferation and migration

Stimulation of adult neurogenesis from endogenous neural stem cells has enormous potential for regenerative therapies in the central nervous system. However, the methods used are often invasive and limited in studying dynamic processes. To overcome this, novel techniques and contrast mechanisms for in vivo imaging of neurogenesis have recently been developed and successfully applied – this article reviews the major categories. [14]

Isotope labeling experiments in metabolomics and fluxomics

For both metabolomics and fluxomics, isotopes are increasingly used to unravel structures and activities of cellular networks and their regulation, to investigate mechanisms of diseases and toxicity, and to improve producing strains among other applications. This review article focuses primarily on studies applying stable isotopes and using mass spectrometry, including the underlying principles, experimental and computational methods used, and examples of application. [15]


2nd European Congress on Applied Biotechnology (ECAB)

The European Section of Biochemical Engineering Sciences (ESBES) was established in 1995 to stimulate the communication, education and scientific activities in Biochemical Engineering. Currently ESBES gathers in the same platform members from academia and industry in active collaboration in various fields of applied biosciences and biotechnology fostering advances in several engineering topics.

ESBES became an associated session in the European Federation of Chemical Engineering (EFCE). In this joint venture ESBES brings to the chemical engineering community the knowledge and expertise in bio-related processing. The first result of this association was the organization of the 1st European Congress of Applied Biotechnology (ECAB) together with the 8th ECCE symposium in Berlin, September 2011. The traditional topics of ECCE were thus extended to include biorefineries, bioprocess engineering, bioseparations, biofuels, biomaterials, algae photobiotechnology, bio-based products and nanobiotechnology among other bioenginnering topics.

The great success of the ESBES association with EFCE is the basis for the organization of the 9th ECCE and the 2nd ECAB.

Under the subject Shaping a sustainable future: a partnership of academia, industry and society, the 2nd ECAB will focus on: society, energy, biomedical engineering, food & agro, product engineering & novel materials, biotechnology, bioreactor engineering, analytical technologies, separations & downstream processing, renewable energy & feedstock, processes for bulk & fine chemicals, modelling & simulation, fundamentals, and process intensification

We encourage submissions to the ECAB from all colleagues working or with interest in bridging chemical engineering, biotechnology and biochemical engineering. As Chairmen of the ESBES I encourage you to participate in the ECAB.

Prof. Guilherme N.M. Ferreira, ESBES Chair / University of Algarve, Portugal.

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Biotechnology Journal is the official journal of ESBES.


Skills versus knowledge

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Scientists and “soft” skills are like water and fire. Complementary skills are sometimes considered non-scientific, but this is not to say that academia does not benefit from scientists with excellent communication, problem solving, presentation, business skills, etc. And scientists do have these skills – but often do not really know how to feature these on their profile or CV. This is definitely a critical point when a scientist applies for a position beyond academia – the further away from research, the more emphasis is placed on soft skills (see figure). This is succinctly analyzed in the book “Career Planning for Research Bioscientists” by Sarah Blackford (published by Wiley-Blackwell in October 2012).

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There are professional methods such as Myers Briggs™ to analyze your soft skills, which require a trained and certified person to perform. Some basic tools are freely available online for a scientist to do a self-assessment of skills, values and interests, and match these to a suitable career path. The US National Postdoc Association created an overview of soft skills scientists should have and ScienceCareers has assembled these in a free online self-assessment tool: “My Individual Development Plan” (myIDP). This planner will also match your skills, interests and values with the 20 career categories.

You have to recognize your skills before you can improve and feature them: this is why it is helpful to learn to give and receive feedback in your everyday life. A good method is also to list stories of situations you dealt with in professional and private settings. These stories are a way to find out more about your skills, and also excellent proof of what you can offer to a future employer. You can learn to communicate in theory, but showing what you do in practice is far more convincing! /bj

Barbara Janssens is PhD Careers Manager at the German Cancer Research Center


B&B 2013 Gaden Award Winner

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Congratulations to Kim O'Connor, Professor, Tulane University, winner of the B&B 2013 Gaden Award for her article: Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency. The award presentation and address will be held at an American Chemical Society (ACS), Division of Biochemical Technology (BIOT) session at the April, 2013 ACS National Meeting & Exposition in New Orleans, Louisiana.

B&B 2013 Daniel I. C. Wang Award Winner

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Hal Alper, Assistant Professor, Department of Chemical Engineering, The University of Texas at Austin is the 2013 recipient of the B&B Daniel I.C. Wang Award. This annual award honors a young investigator who has demonstrated a sustained commitment to Biotechnology and Bioengineering and to the growing interdisciplinary community it serves.

Eppendorf Award – call for entries

Until 15 January 2013, young researchers working in Europe who are not older than 35 years are invited to apply for the Eppendorf Award for Young European Investigators. This prize was first established in 1995. It acknowledges outstanding contributions to biomedical research in Europe based on methods of molecular biology, including novel analytical concepts. The winner is selected by an independent expert committee chaired by Reinhard Jahn (Max Planck Institute for Biophysical Chemistry, Göttingen, Germany). Get more information at

More industry news from G.I.T. Laboratory Journal Europe.

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