BiotecVisions 2012, June

Special Edition: Stem cells, Nanobiotech, Synthetic Biology

original image

Editors: Judy Peng /jp; Uta Göbel /ug; Lucie Kalvodova /lk


Contributors: Adrian Miller /ami; Andrea Modica /amo; Anja Stephan /as; Barbara Janssens /bj; Bill Mullen /bm; Danny Asling /da; Fran Harding /fh; Kerstin Brachhold /kb; Luaine Bandounas /lb; Meghana Hemphill /mh; Mia Ricci /mr; Sarah Hayton /sh; Vivian Killet /vk

Sign-up for the Newsletter:

Current event

IUBS: General Assembly and Conferences on Biological Sciences and Bioindustry

July 5–9, 2012

original image

The International Union of Biological Sciences (IUBS) will hold its 31st General Assembly (GA) on July 5–9, 2012 in Suzhou, China. The co-hosts are the Bureau of Life Sciences and Biotechnology, the Chinese Academy of Sciences (CAS), the Bureau of International Cooperation, the Department of International Affairs, and the Association for Science and Technology, China. The theme of the conference is “Promoting Biological Sciences for a Better Life”.

The IUBS was founded in 1919 and it is a non-governmental, non-profit organization that serves as an umbrella organization for a large number of scientific organizations. Currently, there are 29 ordinary members and 80 scientific members. The GA convenes every three years whereat, decisions on the priorities of the IUBS are made, recommendations to the scientific committee are put forward, and elections of executive committee (EC) members and administrative officers are held.

The IUBS is the only international body that covers all disciplines of biological sciences. Thus, the IUBS will also host and organise an international symposium in tandem with the GA so as to provide an opportunity for the international biological community to exchange information, discuss interdisciplinary studies, and promote international collaboration in scientific research programs.

In the 21st century, particularly in recent years, biological sciences and biotechnologies are playing key roles in shaping the world's economy. Bioindustry is also emerging as a new driving force of the world's economic growth and recovery, especially after the recent world financial crisis. To a greater extent, the development of bioindustry is bringing new hope to initiatives in food safety, clean energy and healthy environments. With these circumstances in mind, the IUBS, during this GA, will endeavor to promote collaborations between institutions, companies and scientists, and to push forward the development of bioindustry and bioeconomy by organizing special sessions on bioindustry.

Getting published

What is the impact factor?

original image

When talking about a journal, one of the first questions is: “What is the impact factor?” But, what does this number actually mean? Many experienced researchers are unable to explain this and quite often, even professional editors are not aware of the fine details within the calculations that leads to the impact factor (IF).

Usually in June of each year, Thomson Reuters releases the Journal Citation Report®, which includes the IF of all journals included in the Science Citation Index® and the Science Citation Index Expanded®.

How is the IF calculated?

When thinking about IF, it is helpful to think in three-year terms: i.e. IF in 2011

equation image


Journal of xxx publishes 75 articles in 2009 and 83 articles in 2010. In 2011 it receives a total of 344 citations to these articles. The journal's IF for 2010 is:

equation image

What does the IF say about a journal?

The above suggests that article published in 2010 or 2009 in a journal with an IF of 2.18 will be cited on average 2.18 times 2011; however, it may be that articles published in 2009 and 2010 are actually not cited in 2011, while a few other articles are cited 10 times and more, and have more “impact” on the IF. Therefore, it is important to remember that the IF is an average measure and does not necessarily reflect the impact of a particular article in the journal.

Does this mean that not all citations count toward the IF?

This is indeed true. Only citations to articles published in the two previous years are included. When an article published in 2011 cites an article published in 2008 or earlier, this citation will not count for the IF of this journal.

These facts suggest that while IF is commonly used as a measure of the quality of a journal and hence the research it publishes, it is important to keep in mind that the IF is not everything. /ug

Read more about this in previous issues of BiotecVisions on selecting the right target journal and insight into the Editorial Office.

Uta Göbel is Assistant Editor for Biotechnology Journal and also works for Engineering in Life Sciences and edits BiotecVisions.

Cell death predicts stem cell differentiation

Programmed cell death shapes the form of the developing embryo and the process continues throughout life to maintain homeostasis and repair damaged tissue. Recent studies imply that pathways associated with cell death influence the fate of differentiating stem cells. Studying the association of cell death with differentiation, however, has been hampered by the lack of methods to mark dead cells without applying exogenous labels that may alter cell fate. By monitoring the autofluorescent cell metabolite NADH using multi-photon fluorescence microscopy, Buschke and colleagues from the University of Wisconsin, Madison, USA, track cell death within differentiating embryonic stem cell aggregates without disrupting either the cell aggregate or the differentiation process. This non-invasive method allowed a correlation between high levels of cell viability at early stages and high cardiomyocyte yield to be detected. /fh [1]

original image

Rational bioprocess design for human pluripotent stem cell

In this Editor's Choice paper from Biotechnology and Bioengineering, Zandstra and coworkers from Toronto, Canada present a predictive bioprocess design strategy employing cell- and molecular-level analysis of rate-limiting steps in human pluripotent stem cell (hPSC) expansion and differentiation, and apply it to produce definitive endoderm (DE) progenitors using a scalable directed-differentiation technology. The study demonstrates that induced pluripotent stem cell (iPSC) expansion and differentiation conditions can be prospectively specified to guide the enhanced production of target cells in a scale-free directed differentiation system. /mr [2]

original image

New from old: Dedifferentiated aged epidermal cells are a source of skin stem cells

The engineering of skin replacements has been limited by the small numbers of epidermal stem cells yielded from conventional isolation techniques. In a recent article in Aging Cell, Zhang and colleagues from Beijing, China, demonstrate that an abundance of similar cells can be generated from de-differentiated aged epidermal cells. Initially examining the de-differentiation of grafted epidermal sheets in a wound microenvironment, the authors found that inhibiting the Wnt/β-catenin signalling pathway blocked the induction of epidermal stem cell-like cells. In vitro, activation of Wnt signaling was verified to control the de-differentiation process. The principle of using these “induced aged epidermal cells” to manufacture skin replacements is demonstrated through the formation of epidermis from the de-differentiated cells on a dermal equivalent model surface. /fh [3]

original image

Live and in color: Detecting pluripotency in live cells

Alkaline phosphatase is a key marker of pluripotency, and its expression is used to define embryonic, germ and induced pluripotent stem cell populations. Current alkaline phosphatase staining protocols destroy cell integrity and structure, so once a cell is recognized to be pluripotent, it can no longer be expanded in culture. In Stem Cell Reviews and Reports authors from Eugene, OR, and Carlsbad, CA, USA, describe a new fluorogenic substrate for alkaline phosphatase, which allows cells to continue to be cultured after staining. Various mouse and human stem cells could be discriminated from underlying feeder cells using this reagent. Stained stem cell colonies retained their morphology and differentiation potential. This new reagent permits pluripotent cells to be rapidly identified, isolated and expanded, and has additional applications in diagnostics where alkaline phosphatase is used a marker. /fh [4]

original image

Cheaper cytokine production for stem cell cultures

Basic fibroblast growth factor (FGF-2) is a cytokine that is used to keep embryonic stem cells in an undifferentiated state. The application is however limited because of its high price. In Engineering in Life Sciences Thomas Scheper (Hannover, Germany) and collaborators present a fast and efficient process for the production and purification of FGF-2 from recombinant Escherichia coli cultures with reusable membrane adsorbers. After achieving a high expression level of FGF-2 in fed-batch cultivation, a new combination of cation exchange membrane chromatography and heparin-sepharose affinity chromatography is employed to purify the protein. In a polishing step using a novel anion exchange membrane chromatography, endotoxins and DNA are removed. The described process is suitable as a low-cost preparation of bioactive FGF-2 at bench-scale, which can be applied to the production of other cytokines. /ug [5]

original image

Preparation of mammary stem cells

original image

The mammary gland is a complex organ consisting of multiple cell types that undergo extensive remodeling during pregnancy and involution, cyclical changes that suggest the existence of a resident stem cell population that is responsible for remarkable tissue regeneration. The basic functional unit of the mammary gland is the terminal duct lobular unit. Luminal epithelial cells line the ducts while the outer myoepithelial cells secrete the basal lamina that separates the mammary gland parenchyma from the mesenchymal cells of the stroma. Within the epithelial cell population of the ducts reside the mammary gland stem cells and it is believed that this population is the origin of the mammary gland cancer stem cells as well. In the mouse, epithelial stem cells can be separated from mesenchymal cells, allowing for the determination of both normal and cancer stem cell potential of these two populations. /bm [6]

Derivation of cerebellar neurons from hESC

The success of the treatment of cerebellar disorders using hESC-derived neurons depends on efficient differentiation of hESC into functional progenitor cells with specific cell fates, as well as their delivery to specific cerebellar regions. Researchers have recently reported highly efficient generation of functional cerebellar cells from both human and mouse ESCs, using a novel defined culture method. The protocol for this method is based on the application of inductive signaling factors involved in the early patterning of the cerebellar region of the neural tube, followed by the application of factors responsible for cerebellar neuron specification. This protocol is feeder-free, applies human recombinant factors, and produces high yield of desired neurons. /bm [7]

At the central hub: CREB influences a wide spectrum of cell activities

In Bioessays Theo Mantamadiotis et al. (Rio-Patras, Greece and Melbourne, Australia) present an overview over the role of CREB (cAMP response element-binding protein) in neural stem/progenitor cell (NSPC) function and oncogenesis. The transcription factor CREB is not only important for NSPC survival and growth but also regulates the transcription of tumour-promoting genes. A better understanding of the role of CREB and its associated signaling pathways in brain tumor biology will provide an opportunity to investigate novel drug targeting approaches in glioma treatment. /kb [8]

original image

Genome editing in induced pluripotent stem cells

The discovery of induced pluripotent stem (iPS) cells has broadened the promises of regenerative medicine through the generation of syngeneic replacement cells or tissues via the differentiation of patient-specific iPS cells. To apply iPS cell-mediated therapy to patients with genetic disorders, however, genome-editing technologies with high efficiency and specificity are needed. Recently, several targeted genome-editing strategies mediated by zinc finger nuclease (ZFN) and transcription activator-like effector nuclease (TALEN) have been applied to human and mouse iPS cells. Furthermore, spontaneous homologous recombination can restore genotype to wild type in mouse iPS cells heterozygous for genetic mutations. Through genome editing, the clinical application of patient-specific genetic mutation-free iPS cells to genetic disorders can finally be realized. This review in Genes to Cells by authors from Kyoto, Japan, and Beijing, China, introduces recently developed technologies for editing the genome of mouse and human iPS cells carrying pathogenic genetic mutations. /sh [9]

original image

Stem cell plasticity

In the journal EMBO Molecular Medicine authors from Brussels, Belgium, Lausanne, Switzerland, London, UK and Milan, Italy discuss the concept of “plasticity”, defined here as the ability of a cell to change its fate in response to environmental signals. Historical and ethical views are also provided to better understand the modern concept of embryonic or induced stem cells reprogramming. /vk [10]

original image

Tracking stem cells using magnetic nanoparticles

This overview article in WIREs Nanomedicine and Nanobiotechnology by authors from Baltimore, MD, USA, reviews the use of different magnetic nanoparticles and discuss how these particles can be used to track the distribution of transplanted cells in different organ systems. Caveats and limitations inherent to the tracking of nanoparticle-labeled stem cells are also discussed. /mh [11]

original image

Nanomedicine for intracellular therapy

Intracellular pathogens such as Salmonella evade host phagocytic killing by various mechanisms. Classical antimicrobial therapy requires multiple dosages and frequent administration of drugs for a long duration. Intracellular delivery of antimicrobials using nanoparticles may effectively devise therapies for bacterial infections. This review in FEMS Microbiology Letters by authors from the NIH, Bethesda, MD and Virginia Polytechnic Institute and University, Blacksburg, VA, USA, addresses the mechanisms used by Salmonella to avoid host pathogenic killing, reasons for therapeutic failure, and advances in nanoparticle drug delivery technology for efficient intracellular bacterial clearance. /lb [12]

original image

Anti-scorpion toxin nanobody produced in Pichia pastoris

Scorpionism is a life-threating disease occurring mainly in tropical and subtropical regions around the world. Scorpion venom contains highly toxic, small polypeptides diffusing rapidly within the victim and causing serious medical problems. AahI' toxin is the most represented and toxic compound of the Androctonus australis hector venom. Nanobodies have been shown to have advanced features to neutralize these toxins. Previous anti-AahI' nanobodies has been expressed in Escherichia coli. The authors from Universit� de Carthage, Tunis, Tunisia and Universit� Paris Sud Orsay, France, show in this article in the journal Biotechnology and Applied Biochemistry a six-fold increased production in Pichia pastroris in a new glycosylated form. The developed strain facilitates large scale nanobody production n a secreted, soluble and correctly folded form that has high therapeutic potential. /amo [13]

original image

Sensors and switches: Customizing molecular reporting

Microbial small-molecule biosensors and endogenous molecular reporters have a variety of applications includ-ing high-throughput screening of biosynthesis libraries and environmental monitoring. In Biotechnology Journal, Patrick Cirino and colleagues (Houston, TX, USA) review recent efforts in the design and application of customized proteins, RNA molecules, and genetic circuits that control microbial phenotypes in response to specific small molecule stimuli. Examples include altering regulatory protein-effector specificity, engineering new allosteric enzymes, and developing in vivo screening systems for novel riboswitches. The authors focus on microbial screening systems that serve as molecular reporters and facilitate engineering the ligand-binding component to recognize new molecules. /ug [14]

original image

Putting synthesis into biology

The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health; however, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science and across many scales of application. Huimin Zhao and colleagues (University of Illinois at Urbana-Champaign, Urbana, IL, USA) dissect and organize various components of synthetic biology into a coherent picture in this review. /mh [15]

Special issue: CHO cell genomics

Guest editors Michael J. Betenbaugh, Nicole Borth, and Kelvin H. Lee have come together to provide researchers in the CHO community with a set of articles that describe key analysis, genomic tools and resources from the journal Biotechnology and Bioengineering. /mr

original image

Biotechnology essay competition

original image

For this year's World Environment Day (June 5), Biotechnology Journal (BTJ), with the support of its sister journals (Engineering in Life Sciences, Microbial Biotechnology, Biotechnology and Applied Biochemistry, and Biofuels, Bioproducts & Biorefining), is hosting an essay competition under the topic “biotechnology and the green economy”. Young aspiring biotechnologists in secondary schools all over the world are invited to participate in this event and share with us their innovative ideas on the role of biotechnology in the green economy. Three best essays will be selected and published in the forum section of BTJ. /jp

See BTJ forum article for further details.


original image

MaterialsViews is a portal hosted by Wiley and showcases the latest news and events in materials science. /ami

Designing nanomaterials for drug delivery

Researchers at the University of California, Irvine, have developed a new drug-delivery system using protein-based nanoparticles.

Spider made biopolymer for medical applications

Spider silk shows intriguing properties for cell culture. Now, researchers are trying to find the ideal scaffolds for applications in the field of biomedical research and regenerative medicine.


Book review: “Alternative pre-mRNA splicing – Theory and Protocols”

original image

“The book edited by Stefan Stamm, Chris Smith and Reinhard Lührmann, Alternative pre-mRNA splicing, theory and Protocols, has the ambition to provide a very large compendium of both theory and applications in pre-mRNA splicing analysis for all biology and biochemistry investigators and those who wish to enter this wide field.”... for a comprehensive review on this book, see book review by Laurent Corcos and Marine Pesson.

ISBN: 978-3-527-32606-8

Synthetic Biology – Industrial and Environmental Applications

Markus Schmidt

original image

This is the only book to focus on industrial and environmental applications of synthetic biology, covering 17 of the most promising uses in the areas of biofuel, bioremediation and biomaterials. /da

ISBN: 978-3-527-33183-3

Ullmann's – discover a one-of-a-kind reference!

original image

Read a FREE sample article about enzymes...


original image

PhD and then? Interview with a Clinical Research Assistant

After his PhD, Alberto Calabro joined a German company to perform Clinical Research. /bj

Q: Please tell us about what you do?

A: I ensure that all aspects of a specific clinical study are performed by clinical investigators in the best interest of the patients and according to the clinical study protocol. In addition I provide guidance to the personnel involved in the study regarding GCP-ICH regulations and provide solutions for all study-related enquiries.

Q: What do you enjoy most about the job?

A: My tasks vary, from formal duties to practical good sense. I have the opportunity to travel extensively and to meet a great number of people. What I enjoy the most is inherent flexibility required by this job: only a part of the duties can be planned in advance. I must always be ready to review my to-do-list and re-evaluate my priorities.

Q: Are there any aspects you don't enjoy?

A: So far, after two years of clinical monitoring I still enjoy my travel duties, but travel could be demanding. Hitting the road every week could become a disadvantage in the long run.

Q: Why did you decide to move from academia to clinical investigations?

A. My passion for clinical research started during my bachelor studies, during which I worked on not-yet approved medication. Rather than thinking about “leaving” academia, I asked myself why I should continue academic education: I should say my academic training was an excursus that allowed me to acquire the training and experience to successfully understand the scientific background of a clinical study.

Q: Which aspects of your PhD were useful in getting this job?

A: Two things: handling patients' data and organizational tasks in our PhD student association.

Q: What is your tip for PhDs or postdocs?

A: If you are thinking of a career in this direction, follow a GCP-ICH course and contact somebody who has already experience in this sector.

Barbara Janssens is PhD Career Manager at the DKFZ Heidelberg.


WIREs Nanomedicine and Nanobiotechnology

original image

Launched January 2009

2010 Impact Factor 2.189, 2011 Impact Factor coming soon

Authoritative, encyclopedic review publication addressing key topics:

• Toxicology and regulatory issues in nanomedicine

• Implantable materials and surgical technologies

• Diagnostic tools

• Nanotechnology approaches to biology

• Therapeutic approaches and drug discovery

• Biology-inspired nanomaterials

Virtual issues

Nanotechnology and Cancer

Fluorescence in Nanodiagnostics

WIREs Systems Biology and Medicine

original image

Launched July 2009

2011 Impact Factor coming soon

Authoritative, encyclopedic review publication addressing key topics:

• Developmental Biology

• Physiology

• Biological Mechanisms

• Models of Systems Properties and Processes

• Laboratory Methods and Technologies

• Analytical and Computational Methods

• Translational, Genomic and Systems Medicine

Virtual issues

Stem Cells: A Systems Approach

Cancer: A Systems Approach