Genomics and proteomics in process development: opportunities and challenges

Global gene expression profiling by genomic and proteomic analyses has changed the face of drug discovery and biological research in the past few years. The benefit of these technologies in the area of process development for recombinant protein production has been increasingly realized. This review discusses the application of genome-wide expression profiling tools in the design and optimization of bioprocesses, with the emphasis on the effect on process development of mammalian cell culture. Despite the lack of genome sequence information for most of the relevant mammalian cell lines used, these technologies can be applied during various process development steps. Although there are only a few examples in the literature that present a major improvement in productivity based on genomics and proteomics, further advances in analytical tools and genome sequencing technologies will greatly increase our knowledge at the molecular level and will drive the design of future bioprocesses.     

Biofuels in China: opportunities and challenges

With rapid economic development, energy consumption in China has tripled in the past 20 yr, exceeding 2.4 billion tons of standard coal in 2006. The search for new green energy as substitutes for the nonrenewable energy resources has become an urgent task. China has a variety of climates and is rich in potential biofuel plant species. Corn and cassava are used as the main raw materials for bioethanol production in China. At the end of 2005, bioethanol productivity had increased to 1.02 million tons produced by four companies, and bioethanol-blended petrol accounted for 20% of the total petrol consumption in China. According to the Mid- and Long-term Development Plan for Renewable Energy, the consumption of biodiesel in China will reach 0.2 million tons in 2010 and 2.0 million tons in 2020. This review is intended to provide an introduction to the distribution and development of biofuel crops and biofuel industry in China.     

Structural genomics: opportunities and challenges

Following the complete genome sequencing of an increasing number of organisms, structural biology is engaging in a systematic approach of high-throughput structure determination called structural genomics to create a complete inventory of protein folds/structures that will help predict functions for all proteins. First results show that structural genomics will be highly effective in finding functional annotations for proteins of unknown function.     

Protein engineering: opportunities and challenges

The extraordinary properties of natural proteins demonstrate that life-like protein engineering is both achievable and valuable. Rapid progress and impressive results have been made towards this goal using rational design and random techniques or a combination of both. However, we still do not have a general theory on how to specify a structure that is suited to a target function nor can we specify a sequence that folds to a target structure. There is also overreliance on the Darwinian blind search to obtain practical results. In the long run, random methods cannot replace insight in constructing life-like proteins. For the near future, however, in enzyme development, we need to rely on a combination of both.     

Plastics recycling: challenges and opportunities

Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3–4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide.Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel.While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it may be possible to divert the majority of plastic waste from landfills to recycling over the next decades.     

Cassava breeding: opportunities and challenges

Although cassava is a major food crop, its scientific breeding began only recently compared with other crops. Significant progress has been achieved, particularly in Asia where cassava is used mainly for industrial processes and no major biotic constraints affect its productivity. Cassava breeding faces several limitations that need to be addressed. The heterozygous nature of the crop and parental lines used to generate new segregating progenies makes it difficult to identify parents with good breeding values. Breeding so far has been mainly based on a mass phenotypic recurrent selection. There is very little knowledge on the inheritance of traits of agronomic relevance. Several approaches have been taken to overcome the constraints in the current methodologies for the genetic improvement of cassava. Evaluations at early stages of selection allow for estimates of general combining ability effect or breeding values of parental lines. Inbreeding by sequential self-pollination facilitates the identification of useful recessive traits, either already present in the Manihot gene pool or induced by mutagenesis.     

Neutrophils and immunity: challenges and opportunities

Scientists who study neutrophils often have backgrounds in cell biology, biochemistry, haematology, rheumatology or infectious disease. Paradoxically, immunologists seem to have a harder time incorporating these host-defence cells into the framework of their discipline. The recent literature discussed here indicates that it is appropriate for immunologists to take as much interest in neutrophils as in their lymphohaematopoietic cousins with smooth nuclei. Neutrophils inform and shape immune responses, contribute to the repair of tissue as well as its breakdown, use killing mechanisms that enrich our concepts of specificity, and offer exciting opportunities for the treatment of neoplastic, autoinflammatory and autoimmune disorders.     

Sugarcane biotechnology: The challenges and opportunities

Summary Commercial sugarcane, belonging to the genus Saccharum (Poaceae), is an important industrial crop accounting for nearly 70% of sugar produced worldwide. Compared to other major crops, efforts to improve sugarcane are limited and relatively recent, with the first introduction of interspecific hybrids about 80 yr ago. Progress in traditional breeding of sugareane, a highly polyploid and frequently aneuploid plant, is impeded by its narrow gene pool, complex genome, poor fertility, and the long breeding/selection cycle. These constraints, however, make sugarcane a good candidate for molecular breeding. In the past decade considerable progress has been made in understanding and manipulating the sugarcane genome using various biotechnological and cell biological approaches. Notable among them are the creation of transgenic plants with improved agronomic or other important traits, advances in genomics and molecular markers, and progress in understanding the molecular aspects of sucrose transport and accumulation. More recently, substantial effort has been directed towards developing sugarcane as a biofactory for high-value products. While these achievements are commendable, a greater understanding of the sugarcane genome, and cell and whole plant physiology, will accelerate the implementation of commercially significant biotechnology outcomes. We anticipate that the rapid advancements in molecular biology and emerging biotechnology innovations would play a significant role in the future sugarcane crop improvement programs and offer many new opportunities to develop it as a new-generation industrial crop.     

Mining bioprocess data: opportunities and challenges

Modern biotechnology production plants are equipped with sophisticated control, data logging and archiving systems. These data hold a wealth of information that might shed light on the cause of process outcome fluctuations, whether the outcome of concern is productivity or product quality. These data might also provide clues on means to further improve process outcome. Data-driven knowledge discovery approaches can potentially unveil hidden information, predict process outcome, and provide insights on implementing robust processes. Here we describe the steps involved in process data mining with an emphasis on recent advances in data mining methods pertinent to the unique characteristics of biological process data.     

PEGylated protein separations: challenges and opportunities

PEGylation, the covalent attachment of polyethylene glycol (PEG) chains to protein, isa promising method for making an efficient protein drug. Several PEGylated protein drugs, such as PEGylated interferons, are already on the market and others are presently in their clinical trials. However, the PEGylation reaction is very product specific so that generalized or platform processes for both reaction and purification have not yet been established. In the current issue of Biotechnology Journal, Günter Allmaier and colleagues report a modified microchip capillary gel electrophoresis (MCGE), which allows for a rapid separation (one minute) of PEGylated proteins of different degrees of PEGylation.     

Inhibiting viral proteases: challenges and opportunities

Inhibitor design against viral targets must take into account the peculiar characteristics of viral biology-in particular, the plasticity of their replicative machinery. This includes maturational cleavage of the polyprotein, which is mediated by virally encoded proteases. Designing against a movable target is particularly challenging, but at the same time it offers new opportunities. Here we describe our experience with the NS3/4A (NS: nonstructural) serine protease of human hepatitis C virus (HCV). By extensive use of combinatorial peptide libraries, various inhibitor types were generated, including product inhibitors, serine traps, P-P' inhibitors, and prime side inhibitors. The latter represent a first case for a serine protease. A key finding, derived from structural studies utilizing these inhibitors, was that NS3 is an induced-fit protease, requiring both the NS4A cofactor protein and the substrate to fully activate its catalytic machinery. In the absence of cofactor and/or substrate, NS3 exists in solution as a large conformational ensemble, which can be matched by a correspondingly large set of peptide inhibitors, each one stabilizing a given conformer. In the perspective of inhibiting viral proteases in general, we suggest that combinatorial ligand ensembles may be a powerful tool, to contrast the adaptive potential of the viral quasispecies.     

Plant molecular farming: opportunities and challenges

Production of foreign molecules in transgenic plants is anticipated to be an alternative to already established, microbial or animal expression systems with lower production costs. This article reviews the different technologies and approaches currently used to produce economically interesting molecules in plants or plant cell cultures, to evaluate their technical feasibility and economic implications, and to assess the potential socioeconomic and environmental impacts deriving from the adoption of molecular farming products.     

GWAS 2011: Opportunities and challenges

The wide adoption of genome-wide association study (GWAS) has dramatically changed the landscape of the genetic studies of human diseases.Banking on the study design that employs large and multiple-independent samples,linkage disequilibrium (LD) -based systematic genome-wide interrogation,and vigorous statistical standard for declaring genetic association,GWAS has greatly advanced the genetic studies of human disease by successfully identifying over 4 thousands of genetic susceptibility SNPs or loci for 210 diseases/traits in human.Besides its unrivaled scientific achievements,GWAS has also transformed the communities of human genetics by stimulating unprecedented broad and large-scale collaboration and data sharing across different groups and countries,which has enabled some mega genetic studies where dozens or hundreds of thousands of samples were investigated through mete-analysis,providing enormous statistical power for discovering genetic variants,even the ones with very moderate effect on disease phenotype or physiological trait.While the success of GWAS has been widely recognized,there are many concerns on GWAS that are being passionately debated.In particular,there ate heated discussions on why only a limited proportion,quiet often a small proportion,of genetic heritability can be explained by the GWAS findings,and whether and how the GWAS findings have really advanced the biological investigation and understanding of disease mechanisms.Concerning these shortcomings of GWAS,many have genuinely questioned the perspective of translating the GWAS findings into clinical practice.To provide a platform to discuss the progresses and shortcomings of GWAS,a nature conference,titled “GWAS 2011:Opportunities and Challenges”,was organized through the collaboration between the Nature Genetics and Anhui Medical University,which was held in Hefei,China on May 19-21,2011.     

Modifier genetics in neuropsychiatric disease: challenges and opportunities

A new study focuses attention on multigenic interactions influencing the risk of autism spectrum disorders.     

Population viability analyses in plants: challenges and opportunities

This review of 95 plant population viability analyses (PVAs) reveals that most studies consider one species, only a few populations and are based on data collected for less than five years. Only five studies referred to themselves as PVAs. Plants offer numerous challenges, such as seed banks and periodic recruitment, but these can be answered with suitable data collection and modeling. New approaches, such as metapopulation models, inclusion of disturbance cycles, and integration of genetics and demography, are producing more realistic PVAs. Although exact solutions are fraught with limitations, plant PVAs can be useful in comparing management regimes, populations and microhabitats, and in using these results to guide conservation and management.     

Zebrafish heart failure models: opportunities and challenges

Heart failure is a complex pathophysiological syndrome of pumping functional failure that results from injury, infection or toxin-induced damage on the myocardium, as well as genetic influence. Gene mutations associated with cardiomyopathies can lead to various pathologies of heart failure. In recent years, zebrafish, Danio rerio, has emerged as an excellent model to study human cardiovascular diseases such as congenital heart defects, cardiomyopathy, and preclinical development of drugs targeting these diseases. In this review, we will first summarize zebrafish genetic models of heart failure arose from cardiomyopathy, which is caused by mutations in sarcomere, calcium or mitochondrial-associated genes. Moreover, we outline zebrafish heart failure models triggered by chemical compounds. Elucidation of these models will improve the understanding of the mechanism of pathogenesis and provide potential targets for novel therapies.