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From stem cells and cadaveric matrix to engineered organs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The definitive treatment for end-stage heart failure, organ transplant, is limited by the supply of donor organs. Successful allograft recipients suffer significant adverse effects from chronic antirejection medications. Positive clinical treatment of injured myocardium with stem/progenitor cells has led to hope that one day autologous stem-cell-derived whole or partial donor organs can be generated. Advances in the ability to isolate (or generate) stem or progenitor cells that can give rise to beating cardiocyte-like cells and vascular components, and the advent of human iPS cell technology when combined with recent a...
Source: Current Opinion in Biotechnology - November 12, 2009 Category: Biotechnology Authors: Taylor DA Tags: Curr Opin Biotechnol Source Type: journals

Syntrophy in Anaerobic Global Carbon Cycles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Syntrophy is an essential intermediary step in the anaerobic conversion of organic matter to methane where metabolically distinct microorganisms are tightly linked by the need to maintain the exchanged metabolites at very low concentrations. Anaerobic syntrophy is thermodynamically constrained, and is probably a prime reason why it is difficult to culture microbes as these approaches disrupt consortia. Reconstruction of artificial syntrophic consortia has allowed uncultured syntrophic metabolizers and methanogens to be optimally grown and studied biochemically. The pathways for syntrophic acetate, propionate and longer...
Source: Current Opinion in Biotechnology - November 6, 2009 Category: Biotechnology Authors: McInerney MJ, Sieber JR, Gunsalus RP Tags: Curr Opin Biotechnol Source Type: journals

Tissue, cell and pathway engineering.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19897354 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - November 6, 2009 Category: Biotechnology Authors: Chandran S, Naughton GK Tags: Curr Opin Biotechnol Source Type: journals

Chemical biotechnology: an expanding discipline that contributes to sustainable development in the 21st century.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19897355 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - November 6, 2009 Category: Biotechnology Authors: Watanabe K, Bennett G Tags: Curr Opin Biotechnol Source Type: journals

Engineering organs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Applications of regenerative medicine technology may offer novel therapies for patients with injuries, end-stage organ failure, or other clinical problems. Currently, patients suffering from diseased and injured organs can be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and m...
Source: Current Opinion in Biotechnology - November 5, 2009 Category: Biotechnology Authors: Atala A Tags: Curr Opin Biotechnol Source Type: journals

Discovery and development of biopharmaceuticals: current issues.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The establishment of recombinant DNA technologies in the past several decades has made it possible to develop a wide variety of therapeutic proteins to address a corresponding variety of unmet medical needs. Therapeutic proteins have had a major impact on health care, and are likely to grow in importance in the future. As the field of biotherapeutics evolves, there are many current and future challenges to be met. A highly competitive environment has emerged, in many cases with multiple products designed to modulate the same therapeutic target or pathway. The competition is resulting in more effective therapeutics as t...
Source: Current Opinion in Biotechnology - November 5, 2009 Category: Biotechnology Authors: Strohl WR, Knight DM Tags: Curr Opin Biotechnol Source Type: journals

The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dose selection for first-in-human (FIH) clinical trials with monoclonal antibodies (mAbs) is based on specifically designed preclinical pharmacology and toxicology studies, mechanistic ex vivo/in vitro investigations with human and animal cells and pharmacokinetic/pharmacodynamic (PK/PD) modeling approaches and requires a thorough understanding of the biology of the target and the relative binding and pharmacological activity of the mAb in animals and humans. These investigations provide the essential information required for the selection of a safe starting dose and escalation for FIH trials based on toxicology and ph...
Source: Current Opinion in Biotechnology - November 5, 2009 Category: Biotechnology Authors: Muller PY, Milton M, Lloyd P, Sims J, Brennan FR Tags: Curr Opin Biotechnol Source Type: journals

Multipotent skin-derived precursors: from biology to clinical translation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Skin-derived precursor cells (SKPs) are a novel population of neural crest-related precursor cells that can be isolated from embryonic and adult skin. SKPs are capable of generating neuronal, glial and mesodermal progeny. Fate mapping and microdissection experiments have demonstrated a neural crest origin of SKPs within defined niches in adult skin. The finding that SKP derivatives such as Schwann cells and neuronal cells have in vitro and in vivo function raises the possibility of SKPs being both an experimental and therapeutic resource for disease modelling and regenerative medicine. This review focuses on the increa...
Source: Current Opinion in Biotechnology - November 5, 2009 Category: Biotechnology Authors: Hunt DP, Jahoda C, Chandran S Tags: Curr Opin Biotechnol Source Type: journals

Optimization of Fc-mediated effector functions of monoclonal antibodies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The engineering of therapeutic and clinical candidate monoclonal antibodies and Fc fusion proteins is becoming more sophisticated at generating molecules that are better suited to the pharmacological activity required of them. There are at least 14 marketed and clinical candidate antibodies and Fc fusion proteins in which the Fc has been modified, either via changes in amino acid sequence or in glycoforms. Recent research and development activities in Fc engineering to generate 'fit-for-purpose' antibodies and Fc fusion proteins are reviewed. PMID: 19896358 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - November 4, 2009 Category: Biotechnology Authors: Strohl WR Tags: Curr Opin Biotechnol Source Type: journals

Safety of biologics, lessons learnt from TGN1412.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In 2006, a first-in-man phase-I clinical trial of an immunomodulatory mAb, TGN1412, ended in disaster when six healthy recipients suffered a life-threatening systemic inflammatory response, termed a 'Cytokine Storm'. A subsequent investigation concluded that these serious adverse events, not predicted by pre-clinical safety testing, were unforeseen biological effects in man. However, the adverse events had been exacerbated by administration of a near-maximum immuno-stimulatory dose to volunteers, because the calculation of a safe starting dose in man had been based upon results from pre-clinical safety testing in a non...
Source: Current Opinion in Biotechnology - November 3, 2009 Category: Biotechnology Authors: Stebbings R, Poole S, Thorpe R Tags: Curr Opin Biotechnol Source Type: journals

B-1 cells and naturally occurring antibodies: influencing the immunogenicity of recombinant human therapeutic proteins?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recombinant human therapeutic proteins are increasingly being used to treat serious and life-threatening diseases like multiple sclerosis, diabetes mellitus, and cancer. An important side effect of these proteins is the development of antidrug antibodies, which can be neutralizing and thus interfere with the efficacy and safety of the drug. Some biophysical properties, for example, aggregation, also can initiate the immunogenic response to human therapeutics. Many other factors including patients' characteristics may influence this response. Besides induced antibodies, autoantibodies (i.e. naturally occurring antibodie...
Source: Current Opinion in Biotechnology - November 3, 2009 Category: Biotechnology Authors: Sauerborn M, Schellekens H Tags: Curr Opin Biotechnol Source Type: journals

Pharmacological significance of glycosylation in therapeutic proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glycoproteins represent the major share of marketed and clinical development phase therapeutic proteins. A thorough understanding of the nature and function of the carbohydrate moiety and its impact on pharmacology properties is essential in discovering and developing safe and efficacious glycoprotein biopharmaceuticals. This review summarizes the processes of N-linked and O-linked glycosylation and both established and emerging platforms for expression of recombinant glycoproteins. Recent or illustrative examples of N-linked and/or O-linked glycosylation impacting drug pharmacology properties (including activity, phar...
Source: Current Opinion in Biotechnology - November 3, 2009 Category: Biotechnology Authors: Li H, d'Anjou M Tags: Curr Opin Biotechnol Source Type: journals

Receptor-Fc fusion therapeutics, traps, and MIMETIBODY technology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fc fusion proteins are molecules in which the immunoglobulin Fc is fused genetically to a protein of interest, such as an extracellular domain of a receptor, ligand, enzyme, or peptide. Fc fusion proteins have some antibody-like properties such as long serum half-life and easy expression and purification, making them an attractive platform for therapeutic drugs. Five Fc fusion based drugs are on the market presently, and many more are in different stages of clinical trials, demonstrating that Fc fusion proteins have become credible alternatives to monoclonal antibodies as therapeutics. This review summarizes the Fc fus...
Source: Current Opinion in Biotechnology - November 2, 2009 Category: Biotechnology Authors: Huang C Tags: Curr Opin Biotechnol Source Type: journals

Expression systems for therapeutic glycoprotein production.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There are slightly over 165 recombinant pharmaceuticals currently approved for human use. Another 500 protein candidates are in preclinical and clinical development, about 70% of these being glycosylated proteins. The need for expression systems allowing the efficient manufacturing of high quality glycoproteins is thus becoming imperative. Recent developments with CHO cells, the predominant mammalian expression system, have focused on either increasing cell specific productivity or prolonging the life span of cells in culture that translates to high integrated viable cell densities. These two factors have allowed volum...
Source: Current Opinion in Biotechnology - November 2, 2009 Category: Biotechnology Authors: Durocher Y, Butler M Tags: Curr Opin Biotechnol Source Type: journals

Arsenic metabolism by microbes in nature and the impact on arsenic remediation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In nature, both prokaryotes and eukaryotes have evolved a wide spectrum of pathways such as oxidation/reduction, compartmentalization, exclusion, and immobilization [16] as the main natural defense mechanisms to arsenic. This review highlights our current understanding of the biochemistry and molecular biology involved in these natural arsenic metabolisms, and some successful examples of engineered microbes by harnessing these natural mechanisms for effective remediation. PMID: 19880307 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - October 30, 2009 Category: Biotechnology Authors: Tsai SL, Singh S, Chen W Tags: Curr Opin Biotechnol Source Type: journals

Formulation and manufacturability of biologics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An important challenge in the pharmaceutical development of a biologic is the optimization of safety and efficacy while ensuring the ability to manufacture the drug while maintaining quality and stability. The manufacturing process consists of several operational steps referred to as 'unit operations' where the biologic is subjected to different stresses and conditions that may compromise quality and stability. Moreover, recently the requirement for the development of subcutaneous formulations for high dose drugs, such as monoclonal antibodies, at high protein concentrations has created additional challenges for many o...
Source: Current Opinion in Biotechnology - October 30, 2009 Category: Biotechnology Authors: Shire SJ Tags: Curr Opin Biotechnol Source Type: journals

Stem cells in musculoskeletal engineered tissue.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19879127 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - October 28, 2009 Category: Biotechnology Authors: Deans TL, Elisseeff JH Tags: Curr Opin Biotechnol Source Type: journals

Rhizosphere chemical dialogues: plant-microbe interactions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Every organism on earth relies on associations with its neighbors to sustain life. For example, plants form associations with neighboring plants, microflora, and microfauna, while humans maintain symbiotic associations with intestinal microbial flora, which is indispensable for nutrient assimilation and development of the innate immune system. Most of these associations are facilitated by chemical cues exchanged between the host and the symbionts. In the rhizosphere, which includes plant roots and the surrounding area of soil influenced by the roots, plants exude chemicals to effectively communicate with their neighbor...
Source: Current Opinion in Biotechnology - October 27, 2009 Category: Biotechnology Authors: Badri DV, Weir TL, van der Lelie D, Vivanco JM Tags: Curr Opin Biotechnol Source Type: journals

Production of aromatic compounds in bacteria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aromatic class of chemicals includes a large number of industrially important products. In bacteria and plants, the shikimate pathway and related biosynthetic pathways are a source of aromatic compounds having commercial value. Bacterial strains for the production of aromatic compounds from simple carbon sources as raw material have been generated by applying metabolic engineering and random/combinatorial strategies that modify central metabolism, aromatic biosynthetic pathways, transport, and regulatory functions. These strategies are complemented with heterologous gene expression and protein engineering. Engineer...
Source: Current Opinion in Biotechnology - October 27, 2009 Category: Biotechnology Authors: Gosset G Tags: Curr Opin Biotechnol Source Type: journals

Overcoming self-destruction in the pancreas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type 1 diabetes (T1D) is an autoimmune disease where insulin producing pancreatic beta cells are progressively destroyed. In the absence of a cure, exogenous insulin is given to maintain glucose homeostasis. Tolerogenic strategies to halt destruction and facilitate recovery of beta cells are being explored. This disease is under polygenic control; the identification of specific candidate pathways to target for drug discovery or corrective therapy would enhance therapeutic options. Whilst islet transplantation combined with immune suppression has shown some efficacy, the availability of beta cells restricts its general ...
Source: Current Opinion in Biotechnology - October 24, 2009 Category: Biotechnology Authors: Nichols J, Cooke A Tags: Curr Opin Biotechnol Source Type: journals

What can metabolomics learn from genomics and proteomics?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
After nearly a decade, metabolomics has begun to acquire some credence in the scientific community although its acceptance cannot be compared with that of its forerunners, genomics and proteomics. The legitimization of metabolomics as a valid scientific entity depends on the size of the research community it influences. By far the most effective medium for inoculation is the web infrastructure: public servers that accommodate experimental data, simple formats and guidelines for their interpretation, and connectivity between data and tools for analysis. When these elements satisfy the condition to initiate a social epid...
Source: Current Opinion in Biotechnology - October 20, 2009 Category: Biotechnology Authors: Arita M Tags: Curr Opin Biotechnol Source Type: journals

Functional metagenomics for enzyme discovery: challenges to efficient screening.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metagenomics has emerged as an alternative approach to conventional microbial screening that allows exhaustive screening of microbial genomes in their natural environments. Despite the potential usefulness of this approach, functional analysis of the metagenome is often problematic because of insufficient and biased expression of the cloned genes in Escherichia coli. This review highlights recent studies on the screening of metagenomic libraries and discusses some possible solutions for overcoming the expression problem in function-based screening. PMID: 19850467 [PubMed - as supplied by publisher] (Source: Current...
Source: Current Opinion in Biotechnology - October 20, 2009 Category: Biotechnology Authors: Uchiyama T, Miyazaki K Tags: Curr Opin Biotechnol Source Type: journals

Stem cells and liver repair.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The liver has considerable inherent regenerative capacity through hepatocyte division and hepatic progenitor cell proliferation. In chronic disease regeneration eventually fails and liver transplantation is the only curative treatment. Current work aims to restore liver mass and functionality either through transplantation of stem cell derived hepatocyte-like cells or by stimulating endogenous liver repair. Human embryonic stem cells (ESCs) and adult somatic cells can be differentiated into hepatocyte-like cells with potential use in drug testing, bio-artificial livers and transplantation. These cells still have some l...
Source: Current Opinion in Biotechnology - October 15, 2009 Category: Biotechnology Authors: Kung JW, Forbes SJ Tags: Curr Opin Biotechnol Source Type: journals

New strategies to generate induced pluripotent stem cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Direct reprogramming of somatic cells to a pluripotent state, substantiated only three years prior, is one of the most rapidly developing areas of stem cell research. The generation of patient-derived pluripotent cells applicable to disease modelling, drug screening, toxicology tests and, ultimately, autologous cell-based therapies, has the potential to revolutionize medicine. Since 2006, when Takahashi and Yamanaka first reported the generation of induced pluripotent stem cells from murine fibroblasts via retroviral transduction of a defined set of transcription factors, various new methods have been developed to refi...
Source: Current Opinion in Biotechnology - October 15, 2009 Category: Biotechnology Authors: O'Malley J, Woltjen K, Kaji K Tags: Curr Opin Biotechnol Source Type: journals

Stem cells and spinal cord regeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cell-based transplantation strategies are inherently combination therapies, as they may mediate spinal cord repair via trophic or phenotypic mechanisms. The growth factor expression profile and phenotype of transplanted cells are determined by the transplant population as well as by the site into which they are transplanted. Identifying the key pathways involved in transplant survival and differentiation, as well as neuroprotection and regeneration of endogenous tissue, will enable manipulation of both the transplanted cells and the microenvironment to improve transplant efficiency. High purity populations derived from...
Source: Current Opinion in Biotechnology - October 14, 2009 Category: Biotechnology Authors: Rossi SL, Keirstead HS Tags: Curr Opin Biotechnol Source Type: journals

New technologies in limbal epithelial stem cell transplantation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Destruction of the limbal epithelial stem cell (LESC) population in the cornea can lead to disorders that result in chronic inflammation, pain and impaired vision. Amniotic membrane (AM) is commonly used as a substrate for LESC transplantation for ocular surface repair but it is not an ideal substrate and so attempts have been made to find a more suitable alternative. The possible substitutes reviewed here include modified AM, cell carriers such as contact lenses or gauze as well as natural substrates fibrin and silk fibroin and many collagen-based scaffolds. Although there are a number of interesting systems in develo...
Source: Current Opinion in Biotechnology - October 12, 2009 Category: Biotechnology Authors: Levis H, Daniels JT Tags: Curr Opin Biotechnol Source Type: journals

Electron shuttles in biotechnology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Electron-shuttling compounds (electron shuttles [ESs], or redox mediators) are essential components in intracellular electron transfer, while microbes also utilize self-produced and naturally present ESs for extracellular electron transfer. These compounds assist in microbial energy metabolism by facilitating electron transfer between microbes, from electron-donating substances to microbes, and/or from microbes to electron-accepting substances. Artificially supplemented ESs can create new routes of electron flow in the microbial energy metabolism, thereby opening up new possibilities for the application of microbes to ...
Source: Current Opinion in Biotechnology - October 12, 2009 Category: Biotechnology Authors: Watanabe K, Manefield M, Lee M, Kouzuma A Tags: Curr Opin Biotechnol Source Type: journals

Synthetic biology-paths to moving forward.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19822414 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - October 9, 2009 Category: Biotechnology Authors: Weiss R, Panke S Tags: Curr Opin Biotechnol Source Type: journals

Advances in stem cell research for Amyotrophic Lateral Sclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized primarily by motor neuron loss in the motor cortex and spinal cord leading to progressive disability and death. Despite the relative selectivity of motor neuron loss, recent studies have implicated other cell types including astrocytes and microglia as contributors to this cell death. This understanding has resulted in stem-cell-replacement strategies of these cell types, which may result in neuroprotection. In addition to cell-replacement strategies, the development of induced pluripotent stem cell (iPSC) technologies has resulted in the...
Source: Current Opinion in Biotechnology - October 8, 2009 Category: Biotechnology Authors: Papadeas ST, Maragakis NJ Tags: Curr Opin Biotechnol Source Type: journals

Protein technologies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19783134 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - September 24, 2009 Category: Biotechnology Authors: V Wood K, S Tawfik D Tags: Curr Opin Biotechnol Source Type: journals

Tissue-engineered skin substitutes in regenerative medicine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advance in cellular tissue-engineered skin constructs have refined the applications already commercially available, in particular, by the use of genetically modified cells to enhance their properties on the treatment of wounds and to ease the application of epidermis using sprayed keratinocytes. This approach lends itself to use of chimeric epidermis, cultured allogeneic cells, to provide short-term coverage, together with minimally cultured autologous cells for long-term repair. Experimental models of skin include pathological conditions, phenomena such as aging and organogenesis, as in the hair follicle grown ...
Source: Current Opinion in Biotechnology - September 23, 2009 Category: Biotechnology Authors: Mansbridge J Tags: Curr Opin Biotechnol Source Type: journals

Optimizing mesenchymal stem cell-based therapeutics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mesenchymal stem cell (MSC)-based therapeutics are showing significant benefit in multiple clinical trials conducted by both academic and commercial organizations, but obstacles remain for their large-scale commercial implementation. Recent studies have attempted to optimize MSC-based therapeutics by either enhancing their potency or increasing their delivery to target tissues. Overexpression of trophic factors or in vitro exposure to potency-enhancing factors are two approaches that are demonstrating success in preclinical animal models. Delivery enhancement strategies involving tissue-specific cytokine pathways or bi...
Source: Current Opinion in Biotechnology - September 21, 2009 Category: Biotechnology Authors: Wagner J, Kean T, Young R, Dennis JE, Caplan AI Tags: Curr Opin Biotechnol Source Type: journals

Recent advances in mammalian synthetic biology-design of synthetic transgene control networks.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Capitalizing on an era of functional genomic research, systems biology offers a systematic quantitative analysis of existing biological systems thereby providing the molecular inventory of biological parts that are currently being used for rational synthesis and engineering of complex biological systems with novel and potentially useful functions-an emerging discipline known as synthetic biology. During the past decade synthetic biology has rapidly developed from simple control devices fine-tuning the activity of single genes and proteins to multi-gene/protein-based transcription and signaling networks providing new in...
Source: Current Opinion in Biotechnology - September 14, 2009 Category: Biotechnology Authors: Tigges M, Fussenegger M Tags: Curr Opin Biotechnol Source Type: journals

Computational design tools for synthetic biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Computer-aided design, pervasive in other engineering disciplines, is currently developing in synthetic biology. Concepts for standardization and hierarchies of parts, devices and systems provide a basis for efficient engineering in biology. Recently developed computational tools, for instance, enable rational (and graphical) composition of genetic circuits from standard parts, and subsequent simulation for testing the predicted functions in silico. The computational design of DNA and proteins with predetermined quantitative functions has made similar advances. The biggest challenge, however, is the integration of tool...
Source: Current Opinion in Biotechnology - September 13, 2009 Category: Biotechnology Authors: Marchisio MA, Stelling J Tags: Curr Opin Biotechnol Source Type: journals

Docking and chemoinformatic screens for new ligands and targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Computer-based docking screens are now widely used to discover new ligands for targets of known structure; in the last two years alone, the discovery of ligands for more than 20 proteins has been reported. Recently, investigators have also turned to predicting new substrates for enzymes of unknown function, taking docking in a wholly new direction. Increasingly, the hit rates, the true-positives, and the false-positives from the docking screens are being compared to those from empirical, high-throughput screens, revealing the strengths, weaknesses, and complementarities of both techniques. The recent efflorescence of G...
Source: Current Opinion in Biotechnology - September 2, 2009 Category: Biotechnology Authors: Kolb P, Ferreira RS, Irwin JJ, Shoichet BK Tags: Curr Opin Biotechnol Source Type: journals

Engineering multicellular systems by cell-cell communication.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Synthetic biology encompasses the design of new biological parts and systems as well as the modulation of existing biological networks to generate novel functions. In recent years, increasing emphasis has been placed on the engineering of population-level behaviors using cell-cell communication. From the engineering perspective, cell-cell communication serves as a versatile regulatory module that enables coordination among cells in and between populations and facilitates the generation of reliable dynamics. In addition to exploring biological 'design principles' via the construction of increasingly complex dynamics, co...
Source: Current Opinion in Biotechnology - September 1, 2009 Category: Biotechnology Authors: Pai A, Tanouchi Y, Collins CH, You L Tags: Curr Opin Biotechnol Source Type: journals

Chemical approaches to synthetic biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The term chemical synthetic biology defines that part of the field that, instead of assuming an engineering approach based on genome manipulation, is oriented towards the synthesis of chemical structures alternative to those present in nature. Several different literature projects will be illustrated, including the two of our group. One is concerned with the 'Never Born Proteins' (NBPs), namely polypeptide sequences that are not present in nature, the other is concerned with the notion of 'minimal cells', semi-synthetic compartments (usually liposomes) containing the minimal and sufficient number of components to perfo...
Source: Current Opinion in Biotechnology - August 31, 2009 Category: Biotechnology Authors: Chiarabelli C, Stano P, Luisi PL Tags: Curr Opin Biotechnol Source Type: journals

RNA-based computation in live cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Man-made molecular 'computers' that operate inside live cells will enable unprecedented level of control over cellular physiology. A promising approach to building these computers uses RNA molecules and RNA-based regulation. RNA naturally lends itself to create 'digital' molecular networks that embody standardized (normal) forms of logic functions. The network's inputs, that may or may not be inverted by single-input NOT logic gates, feed into multi-input AND gates whose outputs are in turn integrated in a multi-input OR gate. Below I review recent steps that have been taken toward implementing these networks with allo...
Source: Current Opinion in Biotechnology - August 28, 2009 Category: Biotechnology Authors: Benenson Y Tags: Curr Opin Biotechnol Source Type: journals

Chemical synthesis using synthetic biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An immense array of naturally occurring biological systems have evolved that convert simple substrates into the products that cells need for growth and persistence. Through the careful application of metabolic engineering and synthetic biology, this biotransformation potential can be harnessed to produce chemicals that address unmet clinical and industrial needs. Developing the capacity to utilize biology to perform chemistry is a matter of increasing control over both the function of synthetic biological systems and the engineering of those systems. Recent efforts have improved general techniques and yielded successes...
Source: Current Opinion in Biotechnology - August 28, 2009 Category: Biotechnology Authors: Carothers JM, Goler JA, Keasling JD Tags: Curr Opin Biotechnol Source Type: journals

Directed evolution: new parts and optimized function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Constructing novel biological systems that function in a robust and predictable manner requires better methods for discovering new functional molecules and for optimizing their assembly in novel biological contexts. By enabling functional diversification and optimization in the absence of detailed mechanistic understanding, directed evolution is a powerful complement to 'rational' engineering approaches. Aided by clever selection schemes, directed evolution has generated new parts for genetic circuits, cell-cell communication systems, and non-natural metabolic pathways in bacteria. PMID: 19720520 [PubMed - as suppl...
Source: Current Opinion in Biotechnology - August 28, 2009 Category: Biotechnology Authors: Dougherty MJ, Arnold FH Tags: Curr Opin Biotechnol Source Type: journals

Designing evolvable libraries using multi-body potentials.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Novel high-throughput technologies for directed evolution enable experimental coverage of an impressive number of sequences. Nevertheless, the success of such experiments hinges on the initial sequence libraries. Here we consider the computational design of smart focused libraries and review insights from experimental strategies and theoretic advances in modelling their energy landscapes. In library design as in structure prediction, the applied energy function is the key. Current knowledge-based potentials have proven more successful than purely physics-based ones. Here we summarize novel approaches that extend the cl...
Source: Current Opinion in Biotechnology - August 24, 2009 Category: Biotechnology Authors: Lappe M, Bagler G, Filippis I, Stehr H, Duarte JM, Sathyapriya R Tags: Curr Opin Biotechnol Source Type: journals

Backbone flexibility in computational protein design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The field of computational protein design has produced striking successes, including the engineering of novel enzymes. Many of these achievements employed methodologies that sample amino acid side-chains on a fixed backbone, while methods that explicitly model backbone flexibility have so far largely focused on the design of new structures rather than functions. Recent methodological improvements in conformational sampling techniques, some borrowed from the field of robotics to model mechanically accessible conformations, now provide exciting opportunities to explore amino acid sequences and backbone structures simulta...
Source: Current Opinion in Biotechnology - August 23, 2009 Category: Biotechnology Authors: Mandell DJ, Kortemme T Tags: Curr Opin Biotechnol Source Type: journals

Engineering next generation proteases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The engineering of novel and precise sequence specificity into proteases will provide an important route to the development of exciting new tools for analytical, biotechnological, and therapeutic applications. Significant progress has been made in reprogramming protease specificity, largely because of the development of high-throughput assay technologies allowing the isolation of protease variants from large libraries. For example, using directed evolution as well as other approaches, proteases have been reprogrammed to cleave substrates containing a variety of amino acids in the P1 and P1' positions including a post-t...
Source: Current Opinion in Biotechnology - August 23, 2009 Category: Biotechnology Authors: Pogson M, Georgiou G, Iverson BL Tags: Curr Opin Biotechnol Source Type: journals

Next generation immunotherapeutics-honing the magic bullet.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most therapeutic antibodies in the clinic today are based on fully humanised immunoglobulins. They have proven to be outstandingly effective, especially for the treatment of cancer, autoimmune and inflammatory diseases where the target is a single, well-defined and accessible molecule. Many diseases however are complex, involving multiple mediators or signalling pathways that could be targeted simultaneously to maximise clinical benefit. There is also a wealth of validated intracellular and CNS-based targets which are currently inaccessible to monoclonal antibody therapy. A spectrum of next generation immunotherapeutic...
Source: Current Opinion in Biotechnology - August 23, 2009 Category: Biotechnology Authors: Enever C, Batuwangala T, Plummer C, Sepp A Tags: Curr Opin Biotechnol Source Type: journals

Engineering DNA processing enzymes for the postgenomic era.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DNA has been a main focus of biomedical research ever since its discovery as the hereditary molecule. This discovery laid the foundation for scientists to begin both to elucidate and to manipulate its function. Since then many DNA processing enzymes have been discovered and many technologies have been developed to process and manipulate DNA with these enzymes. The sequencing of entire genomes has increased the demand for sophisticated DNA processing enzymes. This need is being addressed by engineering DNA processing enzymes using rational and evolutionary approaches to improve or design novel properties. It now appears...
Source: Current Opinion in Biotechnology - August 20, 2009 Category: Biotechnology Authors: Buchholz F Tags: Curr Opin Biotechnol Source Type: journals

Generation of new protein functions by nonhomologous combinations and rearrangements of domains and modules.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Generation of novel protein functions is a major goal in biotechnology and also a rigorous test for our understanding of the relationship between protein structure and function. Early examples of protein engineering focused on design and directed evolution within the constraints of the original protein architecture, exemplified by the highly successful fields of antibody and enzyme engineering. Recent studies show that protein engineering strategies which step away from these natural architectures, that is by manipulating the organization of domains and modules thus mimicking nonhomologous recombination, are highly eff...
Source: Current Opinion in Biotechnology - August 20, 2009 Category: Biotechnology Authors: Koide S Tags: Curr Opin Biotechnol Source Type: journals

Myopic selection of novel information drives evolution.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Synthetic biology aims at reconstructing life. Besides understanding what life is, its ultimate goal is to design cell factories meant to satisfy pressing needs. The success of genome transplantation demonstrates that the cell is split into a machine and a program. The program codes for processes that reproduce the machine and replicate the program. Reproduction is tightly linked to evolution, because the program codes for information trapping. Degradation processes make room to cope with ageing and inaccurate syntheses. Yet they use energy to prevent degradation of functional entities, thus permitting accumulation of ...
Source: Current Opinion in Biotechnology - August 20, 2009 Category: Biotechnology Authors: Danchin A Tags: Curr Opin Biotechnol Source Type: journals

Protein engineering in designing tailored enzymes and microorganisms for biofuels production.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lignocellulosic biofuels represent a sustainable, renewable, and the only foreseeable alternative energy source to transportation fossil fuels. However, the recalcitrant nature of lignocellulose poses technical hurdles to an economically viable biorefinery. Low enzymatic hydrolysis efficiency and low productivity, yield, and titer of biofuels are among the top cost contributors. Protein engineering has been used to improve the performance of lignocellulose-degrading enzymes, as well as proteins involved in biofuel synthesis pathways. Unlike its great success seen in other industrial applications, protein engineering ha...
Source: Current Opinion in Biotechnology - August 3, 2009 Category: Biotechnology Authors: Wen F, Nair NU, Zhao H Tags: Curr Opin Biotechnol Source Type: journals

Engineering algae for biohydrogen and biofuel production.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There is currently substantial interest in utilizing eukaryotic algae for the renewable production of several bioenergy carriers, including starches for alcohols, lipids for diesel fuel surrogates, and H(2) for fuel cells. Relative to terrestrial biofuel feedstocks, algae can convert solar energy into fuels at higher photosynthetic efficiencies, and can thrive in salt water systems. Recently, there has been considerable progress in identifying relevant bioenergy genes and pathways in microalgae, and powerful genetic techniques have been developed to engineer some strains via the targeted disruption of endogenous genes ...
Source: Current Opinion in Biotechnology - June 24, 2009 Category: Biotechnology Authors: Beer LL, Boyd ES, Peters JW, Posewitz MC Tags: Curr Opin Biotechnol Source Type: journals

We march backwards into the future.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19560337 [PubMed - as supplied by publisher] (Source: Current Opinion in Biotechnology)
Source: Current Opinion in Biotechnology - June 24, 2009 Category: Biotechnology Authors: Jeffries T, Lindblad P Tags: Curr Opin Biotechnol Source Type: journals