Reductionism and complexity in molecular biology. Scientists now have the tools to unravel biological and overcome the limitations of reductionism. EMBO Rep

Ecole Supérieure de Biotechnologie de Strasbourg at the Centre National de la Recherche Scientifique (CNRS) in Strasbourg, France.
EMBO Reports (Impact Factor: 9.06). 12/2004; 5(11):1016-20. DOI: 10.1038/sj.embor.7400284
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Available from: Marc H V Van Regenmortel, Sep 28, 2015
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    • "Cancer is the end result of numerous alterations in biochemical pathways and networks [10]. Understanding the molecular perturbations that underlie cancer initiation, progression and metastasis are critical. "
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    ABSTRACT: Despite the lack of agreement on their exact roles, it is known that miRNAs contribute to cancer progression. Many studies utilize methods to detect differential regulation of miRNA expression. It is prohibitively expensive to examine all potentially dysregulated miRNAs and traditionally, researchers have focused their efforts on the most extremely dysregulated miRNAs. These methods may overlook the contribution of less differentially expressed but more functionally relevant miRNAs. The purpose of this study was to outline a method that not only utilizes differential expression but ranks miRNAs based on the functional relevance of their targets. This work uses a networks based approach to determine the sum node degree for all experimentally verified miRNA targets to identify potential regulators of prostate cancer initiation, progression and metastasis. Here, we present a method for identifying functionally relevant miRNAs that contribute to prostate cancer development. This paper shows that miRNAs preferentially regulate highly connected, central proteins within a protein-protein interaction network. Known targets of miRNAs differentially regulated during prostate cancer progression are enriched in pathways with known involvement in tumorigenesis. To demonstrate the applicability of our method, we utilized a unique model of prostate cancer progression to identify five miRNAs that may contribute to the oncogenic state of the cell. Three of these miRNAs have been shown by other studies to have a role in cancer but their exact role in prostate cancer remains undefined. Developing methods to determine which miRNAs to carry forward into biological and biochemical analyses is important as traditional approaches often overlook miRNAs that contribute to oncogenesis. Our method applied to a model of prostate cancer progression was able to identify miRNAs with roles in prostate cancer development.
    BMC Systems Biology 12/2013; 7 Suppl 5(Suppl 5):S3. DOI:10.1186/1752-0509-7-S5-S3 · 2.44 Impact Factor
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    • "Moreover, merely changing a gene, either in the form of adding a human gene to a mouse or knocking out a gene in a mouse, should not be expected to substantially increase the predictive value of mouse models. This has also been confirmed empirically (LeCouter et al. 1998; Zutphen 2000; Morange 2001; Pearson 2002; Nijhout 2003; Van Regenmortel 2004b; Darlison et al. 2005; Shapiro 2007; Kieburtz and Olanow 2007; Young 2008; Enna and Williams 2009; Geerts 2009). "
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    ABSTRACT: We argue that the recommendations made by the Institute of Medicine's 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological and ethical inconsistencies leading to ignorance of potentially unethical practices and policies regarding the use of animals in scientific research.
    Science and Engineering Ethics 04/2013; 20(2). DOI:10.1007/s11948-013-9442-7 · 0.96 Impact Factor
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    • "Reductionist thinking in HIV vaccinology cells (Van Regenmortel, 2004b; O'Malley and Dupré, 2005; Mazzocchi, 2008). Systems biology is an attempt to describe the multiple interactions between all the parts of a biological system by focusing on the dynamics of the entire system (Ideker et al., 2001; Kitano, 2002). "
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    ABSTRACT: This review describes the structure-based reverse vaccinology approach aimed at developing vaccine immunogens capable of inducing antibodies that broadly neutralize HIV-1. Some basic principles of protein immunochemistry are reviewed and the implications of the extensive polyspecificity of antibodies for vaccine development are underlined. Although it is natural for investigators to want to know the cause of an effective immunological intervention, the classic notion of causality is shown to have little explanatory value for a system as complex as the immune system, where any observed effect always results from many interactions between a large number of components. Causal explanations are reductive because a single factor is singled out for attention and given undue explanatory weight on its own. Other examples of the negative impact of reductionist thinking on HIV vaccine development are discussed. These include 1) the failure to distinguish between the chemical nature of antigenicity and the biological nature of immunogenicity, 2) the belief that when an HIV-1 epitope is reconstructed by rational design to better fit a neutralizing Mab, this will produce an immunogen able to elicit Abs with the same neutralizing capacity as the Ab used as template for designing the antigen 3) the belief that protection against infection can be analysed at the level of individual molecular interactions although it has meaning only at the level of an entire organism. The numerous unsuccessful strategies that have been used to design HIV-1 vaccine immunogens are described and it is suggested that the convergence of so many negative experimental results, justifies the conclusion that reverse vaccinology is unlikely to lead to the development of a preventive HIV-1 vaccine. Immune correlates of protection in vaccinees have not yet been identified because this will become feasible only retrospectively once an effective vaccine exists.
    Frontiers in Immunology 07/2012; 3:194. DOI:10.3389/fimmu.2012.00194
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