New and emerging analytical techniques for marine biotechnology

Marine biotechnology is the industrial, medical or environmental application of biological resources from the sea. Since the marine environment is the most biologically and chemically diverse habitat on the planet, marine biotechnology has, in recent years delivered a growing number of major therapeutic products, industrial and environmental applications and analytical tools. These range from the use of a snail toxin to develop a pain control drug, metabolites from a sea squirt to develop an anti-cancer therapeutic, and marine enzymes to remove bacterial biofilms. In addition, well known and broadly used analytical techniques are derived from marine molecules or enzymes, including green fluorescence protein gene tagging methods and heat resistant polymerases used in the polymerase chain reaction. Advances in bacterial identification, metabolic profiling and physical handling of cells are being revolutionised by techniques such as mass spectrometric analysis of bacterial proteins. Advances in instrumentation and a combination of these physical advances with progress in proteomics and bioinformatics are accelerating our ability to harness biology for commercial gain. Single cell Raman spectroscopy and microfluidics are two emerging techniques which are also discussed elsewhere in this issue. In this review, we provide a brief survey and update of the most powerful and rapidly growing analytical techniques as used in marine biotechnology, together with some promising examples of less well known earlier stage methods which may make a bigger impact in the future.     

The regulatory framework for similar biotherapeutic products in Cuba

Biopharmaceuticals make up a significant proportion of medicinal products used for the treatment of diseases such as cancer, arthritis, cardiac dysfunctions and AIDS. Access to therapies based on the use of these products has been limited as a result of the high marketing costs. Cuba has a biopharmaceutical industry with great potential for innovation, capable of developing new products and to produce others, like the biosimilars destined to fulfill the needs of its National Health System. The Center for State Control on the Quality of Drugs (CECMED) the Cuban NRA, is facing the challenge of regulating the approval of biosimilar products manufactured locally. Consequently, CECMED has issued a position paper establishing the basic principles for regulation of these products and a specific guideline on this was elaborated.     

Forest biotechnology: Innovative methods, emerging opportunities

Summary The productivity of plantation forests is essential to meet the future world demand for wood and wood products in a sustainable fashion and in a manner that preserves natural stands and biodiversity. Plantation forestry has enormously benefited from development and implementation of improved silvicultural and forest management practices during the past century. A second wave of improvements has been brought about by the introduction of new germplasm developed through genetics and breeding efforts for both hardwood and conifer tree species. Coupled with the genetic gains achieved through tree breeding, the emergence of new biotechnological approaches that span the fields of plant developmental biology, genetic transformation, and discovery of genes associated with complex multigenic traits have added a new dimension to forest tree improvement programs. Significant progress has been made during the past five years in the area of plant regeneration via organogenesis and somatic embryogenesis (SE) for economically important tree species. These advances have not only helped the development of efficient gene transfer techniques, but also have opened up avenues for deployment of new high-performance clonally replicated planting stocks in forest plantations. One of the greatest challenges today is the ability to extend this technology to the most elite germplasm, such that it becomes an, economically feasible means for large-scale production and delivery of improved planting stock. Another challenge will be the ability of the forestry research community to capitalize rapidly on current and future genomics-based elucidation of the underlying mechanisms for important but complex phenotypes. Advancements in gene cloning and genomics technology in forest trees have enabled the discovery and introduction of value-added traits for wood quality and resistance to biotic and abiotic stresses into improved genotypes. With these technical advancements, it will be necessary for reliable regulatory infrastructures and processes to be in place worldwide for testing and release of trees improved through biotechnology. Commercialization of planting stocks, as new varieties generated through clonal propagation and advanced breeding programs or as transgenic trees with high-value traits, is expected in the near future, and these trees will enhance the quality and productivity of our plantation forests.     

The genetics of uveal melanoma: an emerging framework for targeted therapy

Uveal melanoma is the second most common form of melanoma and the most common primary intraocular malignancy. Until recently, very little was known about the genetics of this aggressive cancer. Mutations in oncogenes and tumor suppressors that are common in other cancers are conspicuously absent in uveal melanoma. In recent years, however, uveal melanoma has begun to yield its secrets, and a fascinating picture is emerging of how it develops and progresses. Mutations in the G(q) alpha subunits, encoded by GNAQ and GNA11, appear to be early or perhaps initiating events that require further mutations for malignant transformation. On the other hand, mutations in the BRCA1-associated protein-1 (BAP1) appear to occur later and demarcate a molecular brink beyond which metastasis becomes highly likely. BAP1 mutations can also occur in the germline, leading to a distinctive cancer predisposition syndrome. These mutations appear to be key events that provide the potential for targeted therapy. This article will review the genetic findings in uveal melanoma over the past two decades and suggest important areas for future work.     

Review on the worldwide regulatory framework for biosimilars focusing on the Mexican case as an emerging market in Latin America

The global biopharmaceutical market is worth over $100 billion USD. Nearly 90% of these products will lose their patent in the next ten years, leading to the commercialization of their subsequent versions, known as ‘biosimilars’. Biosimilars are much more complex molecules than chemically synthesized generics in terms of size, structure, stability, microheterogeneity, manufacture, etc. Therefore, a specific regulatory framework is needed in order to demonstrate their comparability with innovative products, as well as their quality, safety and efficacy. The EU published the first regulatory pathway in 2005 and has approved 14 biosimilars. Mexico has recently developed a clear regulatory pathway for these products. Their legal basis was established in Article 222 Bis of General Law of Health in 2009, clear specifications in the Regulation for Health Goods in 2011, and further requirements in the Mexican Official Norm NOM-EM-001-SSA1-2012. The aim of this review is to summarize the regulatory pathways for biosimilars in the world with a special focus on Mexican experience, so as contribute to the development of regulations in other countries.     

Sortase-mediated protein ligation: an emerging biotechnology tool for protein modification and immobilisation

Sortases are transpeptidases produced by Gram-positive bacteria to anchor cell surface proteins covalently to the cell wall. The Staphylococcus aureus sortase A (SrtA) cleaves a short C-terminal recognition motif (LPXTG) on the target protein followed by the formation of an amide bond with the pentaglycine cross-bridge in the cell wall. Over recent years, several researchers have exploited this specific reaction for a range of biotechnology applications, including the incorporation of non-native peptides and non-peptidic molecules into proteins, the generation of nucleic acid–peptide conjugates and neoglycoconjugates, protein circularisation, and labelling of cell surface proteins on living cells.     

Transducers: an emerging probabilistic framework for modeling indels on trees

Contact: ihh{at}berkeley.edu Associate Editor: Alex Bateman     

Taking the long view: an emerging framework for translational psychiatric science

Understood in their historical context, current debates about psychiatric classification, prompted by the publication of the DSM‐5, open up new opportunities for improved translational research in psychiatry. In this paper, we draw lessons for translational research from three time slices of 20th century psychiatry. From the first time slice, 1913 and the publication of Jaspers' General Psychopathology, the lesson is that translational research in psychiatry requires a pluralistic approach encompassing equally the sciences of mind (including the social sciences) and of brain. From the second time slice, 1959 and a conference in New York from which our present symptom‐based classifications are derived, the lesson is that, while reliability remains the basis of psychiatry as an observational science, validity too is essential to effective translation. From the third time slice, 1997 and a conference on psychiatric classification in Dallas that brought together patients and carers with researchers and clinicians, the lesson is that we need to build further on collaborative models of research combining expertise‐by‐training with expertise‐by‐experience. This is important if we are to meet the specific challenges to translation presented by the complexity of the concept of mental disorder, particularly as reflected in the diversity of desired treatment outcomes. Taken together, these three lessons – a pluralistic approach, reliability and validity, and closer collaboration among relevant stakeholders – provide an emerging framework for more effective translation of research into practice in 21st century psychiatry.     

European regulatory framework and practices for veterinary Leptospira vaccine potency testing

In Europe, the legal basis for requirements for medicinal products is described in the European Pharmacopoeia (Ph. Eur.) In the European Union, the Ph. Eur. is supplemented by several guidelines issued by the European Medicines Agency. Immunological veterinary products must comply with the Ph. Eur. monograph on veterinary vaccines and the accompanying texts, as well as specific monographs. The Ph. Eur. includes monographs on canine leptospirosis and bovine leptospirosis vaccines (inactivated). Both monographs require that an immunogenicity test be performed once in the target species during the life of a vaccine. The hamster challenge test is applied for batch potency testing of canine vaccines. Alternatively, serological tests or suitable validated in vitro tests to determine the content of one or more antigenic components indicative of protection may be performed. Vaccines for use in cattle are tested in a serological test in guinea pigs. The acceptance criteria in alternative tests are set with reference to a batch of vaccine that has given satisfactory results in the immunogenicity test. At a January 2012 European workshop, the suitability of the hamster potency test was questioned and unanimous agreement was reached that moving toward complete in vitro testing is possible and should be promoted.