Computer-aided biotechnology:from immuno-informatics to reverse vaccinology

Genome sequences from many organisms, including humans, have been completed, and high-throughput analyses have produced burgeoning volumes of 'omics' data. Bioinformatics is crucial for the management and analysis of such data and is increasingly used to accelerate progress in a wide variety of large-scale and object-specific functional analyses. Refined algorithms enable biotechnologists to follow 'computer-aided strategies' based on experiments driven by high-confidence predictions. In order to address compound problems, current efforts in immuno-informatics and reverse vaccinology are aimed at developing and tuning integrative approaches and user-friendly, automated bioinformatics environments. This will herald a move to 'computer-aided biotechnology': smart projects in which time-consuming and expensive large-scale experimental approaches are progressively replaced by prediction-driven investigations.

The finance of biotechnology:investment in new biotechnology firms by British venture capitalists-attitudes to, and evaluation of, business proposals

A notable feature of the recent commercialisation of biotechnology has been the success of 200 or so new firms, established in America since 1976, in exploiting specialised market niches. A key factor in their formation has been the ready availability of venture capital funding. These firms have been instrumental in establishing America's lead in exploiting biotechnology. It is this example which Britain has attempted to emulate as part of its strategy for developing its own biotechnology capabilities. This thesis investigated some aspects of the relationship between biotechnology and venture capital, concentrating on the determinants of the venture capitalist's investment decision. Following an extensive literature survey, two hypothetical business proposals were used to find what venture capitalists themselves consider to be the key elements of this decision. It was found that venture capitalists invest in people, not products, and businesses, not industries. It was concluded that venture capital-backed small firms should, therefore, be seen as an adjunct to the development of biotechnology in Britain, rather than as a substitute for a co-ordinated, co-operative strategy involving Government, the financial institutions, industry and academia. This is chiefly because the small size of the UK's domestic market means that many potentially important innovations in biotechnology may continue to be lost, since the short term identification of market opportunities for biotechnology products will dictate that they are insupportable in Britain alone. In addition, the data analysis highlighted some interesting methodological issues concerning the investigation of investment decision making. These related especially to shortcomings in the use of scoresheets and questionnaires in research in this area. The conclusion here was that future research should concentrate on the reasons why an individual reaches an investment decision. It is argued that only in this way can the nature of the evaluation procedures employed by venture capitalists be properly understood.

University-industry-relations - their role in technological innovation:the case of biotechnology in the UK

Biotechnology is one of a series of new `generic technologies' that have been identified by western governments as possessing stategic economic opportunities. In this thesis I examine the characteristics of the technology and the government policies that have been developed to both promote and exploit the underpinning scientific research for biotechnology. The approach I have taken involves an in-depth analysis of the role of university-industry research relations in the development of biotechnology. To this end I carried out a detailed survey of biotechnology companies in the UK on the nature of their interactions and objectives. Through individual case studies of the SERC and DTI club mechanisms in biotechnology, I provide a contemporary appraisal of the development of new mechanisms involving co-ordination and cooperation between industry, government and academia, established to couple state funded science and national economic development. The public policy implications of the club funding systems for science in the UK are examined.

A European competence framework for industrial pharmacy practice in biotechnology

Project Report: The PHAR-IN ("Competences for industrial pharmacy practice in biotechnology") looked at whether there is a difference in how industrial employees and academics rank competences for practice in the biotechnological industry. A small expert panel consisting of the authors of this paper produced a biotechnology competence framework by drawing up an initial list of competences then ranking them in importance using a three-stage Delphi process. The framework was next evaluated and validated by a large expert panel of academics (n = 37) and industrial employees (n = 154). Results show that priorities for industrial employees and academics were similar. The competences for biotechnology practice that received the highest scores were mainly in: . "Research and Development", . "Upstream" and "Downstream" Processing', " . "Product development and formulation", " . "Aseptic processing", ."Analytical methodology", . "Product stability", and . "Regulation". The main area of disagreement was in the category "Ethics and drug safety" where academics ranked competences higher than did industrial employees.

Production of ethanol, organic acids and hydrogen : an opportunity for mixed culture biotechnology?

Peer reviewed

Short-term impact of soybean management on ammonia oxidizers in a Brazilian savanna under restoration as revealed by coupling different techniques

Acknowledgments The authors are very grateful to Mr. Fabiano Bielefeld Nardotto, owner of the Tabapuã dos Pireneus farm, for allowing our free movement around the farm and collection of soil samples, as well as providing information about soybean cultivation. The authors also thank Dr. Plínio de Camargo, who performed the isotopic analysis in the CENA laboratory at the University of São Paulo (USP). This work was supported by grants from the National Council of Technological and Scientific Development (CNPq), Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES), and Foundation for Research Support of Distrito Federal (FAP-DF).

Sortase as a Tool in Biotechnology and Medicine

We have harnessed two reactions catalyzed by the enzyme sortase A and applied them to generate new methods for the purification and site-selective modification of recombinant protein therapeutics.

We utilized native peptide ligation —a well-known function of sortase A— to attach a small molecule drug specifically to the carboxy-terminus of a recombinant protein. By combining this reaction with the unique phase behavior of elastin-like polypeptides, we developed a protocol that produces homogenously-labeled protein-small molecule conjugates using only centrifugation. The same reaction can be used to produce unmodified therapeutic proteins simply by substituting a single reactant. The isolated proteins or protein-small molecule conjugates do not have any exogenous purification tags, eliminating the potential influence of these tags on bioactivity. Because both unmodified and modified proteins are produced by a general process that is the same for any protein of interest and does not require any chromatography, the time, effort, and cost associated with protein purification and modification is greatly reduced.

We also developed an innovative and unique method that attaches a tunable number of drug molecules to any recombinant protein of interest in a site-specific manner. Although the ability of sortase A to carry out native peptide ligation is widely used, we demonstrated that Sortase A is also capable of attaching small molecules to proteins through an isopeptide bond at lysine side chains within a unique amino acid sequence. This reaction —isopeptide ligation— is a new site-specific conjugation method that is orthogonal to all available protein-small conjugation technologies and is the first site-specific conjugation method that attaches the payload to lysine residues. We show that isopeptide ligation can be applied broadly to peptides, proteins, and antibodies using a variety of small molecule cargoes to efficiently generate stable conjugates. We thoroughly assessed the site-selectivity of this reaction using a variety of analytical methods and showed that in many cases the reaction is site-specific for lysines in flexible, disordered regions of the substrate proteins. Finally, we showed that isopeptide ligation can be used to create clinically-relevant antibody-drug conjugates that have potent cytotoxicity towards cancerous cells

The expansion of soybean cultivation in Campeche, México: Problematic and perspectives

The soybean is the grain in which greater food dependency has Mexico, reason why as of 2008, the government has promoted his culture, granting excellent subsidies, as much to producers as to buyers of the grain, thus contributing to a recent process of expansion in certain states, as it happens in Campeche. The objetive of this article is the analysis of the characteristics and effects of those supports, as well as of the rest of factors that until today they have taken to the producers of the mentioned state to initiate or to expand the cultivation of the soybean. The findings of the investigation reveal that although the producers have improved their levels of income, the process is vulnerable, as it depends on variables like the governmental supports, the international prices of the soybean and exchange rate. Although the study of the negative effects of genetically modified soybeans (GM) in other areas (environment, biodiversity, deforestation, human and animal health) is not the purpose of this investigation, some information will be provided, as on the conflict between soybean producers and beekeepers in the state of Campeche.

Analytical strategies for the early quality and safety assurance in the global feed chain. Approaches for nitrogen adulterants in soybean meal and mineral and transformer oils in vegetable oils.

In the past decade, several major food safety crises originated from problems with feed. Consequently, there is an urgent need for early detection of fraudulent adulteration and contamination in the feed chain. Strategies are presented for two specific cases, viz. adulterations of (i) soybean meal with melamine and other types of adulterants/contaminants and (ii) vegetable oils with mineral oil, transformer oil or other oils. These strategies comprise screening at the feed mill or port of entry with non-destructive spectroscopic methods (NIRS and Raman), followed by post-screening and confirmation in the laboratory with MS-based methods. The spectroscopic techniques are suitable for on-site and on-line applications. Currently they are suited to detect fraudulent adulteration at relatively high levels but not to detect low level contamination. The potential use of the strategies for non-targeted analysis is demonstrated.